Variant allele predicted to encode a truncated non-functional protein.
ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.844_850dup (p.Gln284fs)
Germline
Top reviewed classifications are shown here.
Submission summary:
Reviewed by expert panel
Pathogenic
Oct 2016 by
Evidence-based…
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_007294.4(BRCA1):c.844_850dup (p.Gln284fs)
Variation ID: 55735 Accession: VCV000055735.27
- Type and length
-
Duplication, 7 bp
- Location
-
Cytogenetic: 17q21.31 17: 43094680-43094681 (GRCh38) [ NCBI UCSC ] 17: 41246697-41246698 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Apr 4, 2014 Oct 26, 2024 Oct 18, 2016 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_007294.4:c.844_850dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Gln284fs frameshift NM_001407571.1:c.631_637dup NP_001394500.1:p.Gln213fs frameshift NM_001407581.1:c.844_850dup NP_001394510.1:p.Gln284fs frameshift NM_001407582.1:c.844_850dup NP_001394511.1:p.Gln284fs frameshift NM_001407583.1:c.844_850dup NP_001394512.1:p.Gln284fs frameshift NM_001407585.1:c.844_850dup NP_001394514.1:p.Gln284fs frameshift NM_001407587.1:c.841_847dup NP_001394516.1:p.Gln283fs frameshift NM_001407590.1:c.841_847dup NP_001394519.1:p.Gln283fs frameshift NM_001407591.1:c.841_847dup NP_001394520.1:p.Gln283fs frameshift NM_001407593.1:c.844_850dup NP_001394522.1:p.Gln284fs frameshift NM_001407594.1:c.844_850dup NP_001394523.1:p.Gln284fs frameshift NM_001407596.1:c.844_850dup NP_001394525.1:p.Gln284fs frameshift NM_001407597.1:c.844_850dup NP_001394526.1:p.Gln284fs frameshift NM_001407598.1:c.844_850dup NP_001394527.1:p.Gln284fs frameshift NM_001407602.1:c.844_850dup NP_001394531.1:p.Gln284fs frameshift NM_001407603.1:c.844_850dup NP_001394532.1:p.Gln284fs frameshift NM_001407605.1:c.844_850dup NP_001394534.1:p.Gln284fs frameshift NM_001407610.1:c.841_847dup NP_001394539.1:p.Gln283fs frameshift NM_001407611.1:c.841_847dup NP_001394540.1:p.Gln283fs frameshift NM_001407612.1:c.841_847dup NP_001394541.1:p.Gln283fs frameshift NM_001407613.1:c.841_847dup NP_001394542.1:p.Gln283fs frameshift NM_001407614.1:c.841_847dup NP_001394543.1:p.Gln283fs frameshift NM_001407615.1:c.841_847dup NP_001394544.1:p.Gln283fs frameshift NM_001407616.1:c.844_850dup NP_001394545.1:p.Gln284fs frameshift NM_001407617.1:c.844_850dup NP_001394546.1:p.Gln284fs frameshift NM_001407618.1:c.844_850dup NP_001394547.1:p.Gln284fs frameshift NM_001407619.1:c.844_850dup NP_001394548.1:p.Gln284fs frameshift NM_001407620.1:c.844_850dup NP_001394549.1:p.Gln284fs frameshift NM_001407621.1:c.844_850dup NP_001394550.1:p.Gln284fs frameshift NM_001407622.1:c.844_850dup NP_001394551.1:p.Gln284fs frameshift NM_001407623.1:c.844_850dup NP_001394552.1:p.Gln284fs frameshift NM_001407624.1:c.844_850dup NP_001394553.1:p.Gln284fs frameshift NM_001407625.1:c.844_850dup NP_001394554.1:p.Gln284fs frameshift NM_001407626.1:c.844_850dup NP_001394555.1:p.Gln284fs frameshift NM_001407627.1:c.841_847dup NP_001394556.1:p.Gln283fs frameshift NM_001407628.1:c.841_847dup NP_001394557.1:p.Gln283fs frameshift NM_001407629.1:c.841_847dup NP_001394558.1:p.Gln283fs frameshift NM_001407630.1:c.841_847dup NP_001394559.1:p.Gln283fs frameshift NM_001407631.1:c.841_847dup NP_001394560.1:p.Gln283fs frameshift NM_001407632.1:c.841_847dup NP_001394561.1:p.Gln283fs frameshift NM_001407633.1:c.841_847dup NP_001394562.1:p.Gln283fs frameshift NM_001407634.1:c.841_847dup NP_001394563.1:p.Gln283fs frameshift NM_001407635.1:c.841_847dup NP_001394564.1:p.Gln283fs frameshift NM_001407636.1:c.841_847dup NP_001394565.1:p.Gln283fs frameshift NM_001407637.1:c.841_847dup NP_001394566.1:p.Gln283fs frameshift NM_001407638.1:c.841_847dup NP_001394567.1:p.Gln283fs frameshift NM_001407639.1:c.844_850dup NP_001394568.1:p.Gln284fs frameshift NM_001407640.1:c.844_850dup NP_001394569.1:p.Gln284fs frameshift NM_001407641.1:c.844_850dup NP_001394570.1:p.Gln284fs frameshift NM_001407642.1:c.844_850dup NP_001394571.1:p.Gln284fs frameshift NM_001407644.1:c.841_847dup NP_001394573.1:p.Gln283fs frameshift NM_001407645.1:c.841_847dup NP_001394574.1:p.Gln283fs frameshift NM_001407646.1:c.835_841dup NP_001394575.1:p.Gln281fs frameshift NM_001407647.1:c.835_841dup NP_001394576.1:p.Gln281fs frameshift NM_001407648.1:c.721_727dup NP_001394577.1:p.Gln243fs frameshift NM_001407649.1:c.718_724dup NP_001394578.1:p.Gln242fs frameshift NM_001407652.1:c.844_850dup NP_001394581.1:p.Gln284fs frameshift NM_001407653.1:c.766_772dup NP_001394582.1:p.Gln258fs frameshift NM_001407654.1:c.766_772dup NP_001394583.1:p.Gln258fs frameshift NM_001407655.1:c.766_772dup NP_001394584.1:p.Gln258fs frameshift NM_001407656.1:c.766_772dup NP_001394585.1:p.Gln258fs frameshift NM_001407657.1:c.766_772dup NP_001394586.1:p.Gln258fs frameshift NM_001407658.1:c.766_772dup NP_001394587.1:p.Gln258fs frameshift NM_001407659.1:c.763_769dup NP_001394588.1:p.Gln257fs frameshift NM_001407660.1:c.763_769dup NP_001394589.1:p.Gln257fs frameshift NM_001407661.1:c.763_769dup NP_001394590.1:p.Gln257fs frameshift NM_001407662.1:c.763_769dup NP_001394591.1:p.Gln257fs frameshift NM_001407663.1:c.766_772dup NP_001394592.1:p.Gln258fs frameshift NM_001407664.1:c.721_727dup NP_001394593.1:p.Gln243fs frameshift NM_001407665.1:c.721_727dup NP_001394594.1:p.Gln243fs frameshift NM_001407666.1:c.721_727dup NP_001394595.1:p.Gln243fs frameshift NM_001407667.1:c.721_727dup NP_001394596.1:p.Gln243fs frameshift NM_001407668.1:c.721_727dup NP_001394597.1:p.Gln243fs frameshift NM_001407669.1:c.721_727dup NP_001394598.1:p.Gln243fs frameshift NM_001407670.1:c.718_724dup NP_001394599.1:p.Gln242fs frameshift NM_001407671.1:c.718_724dup NP_001394600.1:p.Gln242fs frameshift NM_001407672.1:c.718_724dup NP_001394601.1:p.Gln242fs frameshift NM_001407673.1:c.718_724dup NP_001394602.1:p.Gln242fs frameshift NM_001407674.1:c.721_727dup NP_001394603.1:p.Gln243fs frameshift NM_001407675.1:c.721_727dup NP_001394604.1:p.Gln243fs frameshift NM_001407676.1:c.721_727dup NP_001394605.1:p.Gln243fs frameshift NM_001407677.1:c.721_727dup NP_001394606.1:p.Gln243fs frameshift NM_001407678.1:c.721_727dup NP_001394607.1:p.Gln243fs frameshift NM_001407679.1:c.721_727dup NP_001394608.1:p.Gln243fs frameshift NM_001407680.1:c.721_727dup NP_001394609.1:p.Gln243fs frameshift NM_001407681.1:c.721_727dup NP_001394610.1:p.Gln243fs frameshift NM_001407682.1:c.721_727dup NP_001394611.1:p.Gln243fs frameshift NM_001407683.1:c.721_727dup NP_001394612.1:p.Gln243fs frameshift NM_001407684.1:c.844_850dup NP_001394613.1:p.Gln284fs frameshift NM_001407685.1:c.718_724dup NP_001394614.1:p.Gln242fs frameshift NM_001407686.1:c.718_724dup NP_001394615.1:p.Gln242fs frameshift NM_001407687.1:c.718_724dup NP_001394616.1:p.Gln242fs frameshift NM_001407688.1:c.718_724dup NP_001394617.1:p.Gln242fs frameshift NM_001407689.1:c.718_724dup NP_001394618.1:p.Gln242fs frameshift NM_001407690.1:c.718_724dup NP_001394619.1:p.Gln242fs frameshift NM_001407691.1:c.718_724dup NP_001394620.1:p.Gln242fs frameshift NM_001407692.1:c.703_709dup NP_001394621.1:p.Gln237fs frameshift NM_001407694.1:c.703_709dup NP_001394623.1:p.Gln237fs frameshift NM_001407695.1:c.703_709dup NP_001394624.1:p.Gln237fs frameshift NM_001407696.1:c.703_709dup NP_001394625.1:p.Gln237fs frameshift NM_001407697.1:c.703_709dup NP_001394626.1:p.Gln237fs frameshift NM_001407698.1:c.703_709dup NP_001394627.1:p.Gln237fs frameshift NM_001407724.1:c.703_709dup NP_001394653.1:p.Gln237fs frameshift NM_001407725.1:c.703_709dup NP_001394654.1:p.Gln237fs frameshift NM_001407726.1:c.703_709dup NP_001394655.1:p.Gln237fs frameshift NM_001407727.1:c.703_709dup NP_001394656.1:p.Gln237fs frameshift NM_001407728.1:c.703_709dup NP_001394657.1:p.Gln237fs frameshift NM_001407729.1:c.703_709dup NP_001394658.1:p.Gln237fs frameshift NM_001407730.1:c.703_709dup NP_001394659.1:p.Gln237fs frameshift NM_001407731.1:c.703_709dup NP_001394660.1:p.Gln237fs frameshift NM_001407732.1:c.703_709dup NP_001394661.1:p.Gln237fs frameshift NM_001407733.1:c.703_709dup NP_001394662.1:p.Gln237fs frameshift NM_001407734.1:c.703_709dup NP_001394663.1:p.Gln237fs frameshift NM_001407735.1:c.703_709dup NP_001394664.1:p.Gln237fs frameshift NM_001407736.1:c.703_709dup NP_001394665.1:p.Gln237fs frameshift NM_001407737.1:c.703_709dup NP_001394666.1:p.Gln237fs frameshift NM_001407738.1:c.703_709dup NP_001394667.1:p.Gln237fs frameshift NM_001407739.1:c.703_709dup NP_001394668.1:p.Gln237fs frameshift NM_001407740.1:c.700_706dup NP_001394669.1:p.Gln236fs frameshift NM_001407741.1:c.700_706dup NP_001394670.1:p.Gln236fs frameshift NM_001407742.1:c.700_706dup NP_001394671.1:p.Gln236fs frameshift NM_001407743.1:c.700_706dup NP_001394672.1:p.Gln236fs frameshift NM_001407744.1:c.700_706dup NP_001394673.1:p.Gln236fs frameshift NM_001407745.1:c.700_706dup NP_001394674.1:p.Gln236fs frameshift NM_001407746.1:c.700_706dup NP_001394675.1:p.Gln236fs frameshift NM_001407747.1:c.700_706dup NP_001394676.1:p.Gln236fs frameshift NM_001407748.1:c.700_706dup NP_001394677.1:p.Gln236fs frameshift NM_001407749.1:c.700_706dup NP_001394678.1:p.Gln236fs frameshift NM_001407750.1:c.703_709dup NP_001394679.1:p.Gln237fs frameshift NM_001407751.1:c.703_709dup NP_001394680.1:p.Gln237fs frameshift NM_001407752.1:c.703_709dup NP_001394681.1:p.Gln237fs frameshift NM_001407838.1:c.700_706dup NP_001394767.1:p.Gln236fs frameshift NM_001407839.1:c.700_706dup NP_001394768.1:p.Gln236fs frameshift NM_001407841.1:c.700_706dup NP_001394770.1:p.Gln236fs frameshift NM_001407842.1:c.700_706dup NP_001394771.1:p.Gln236fs frameshift NM_001407843.1:c.700_706dup NP_001394772.1:p.Gln236fs frameshift NM_001407844.1:c.700_706dup NP_001394773.1:p.Gln236fs frameshift NM_001407845.1:c.700_706dup NP_001394774.1:p.Gln236fs frameshift NM_001407846.1:c.700_706dup NP_001394775.1:p.Gln236fs frameshift NM_001407847.1:c.700_706dup NP_001394776.1:p.Gln236fs frameshift NM_001407848.1:c.700_706dup NP_001394777.1:p.Gln236fs frameshift NM_001407849.1:c.700_706dup NP_001394778.1:p.Gln236fs frameshift NM_001407850.1:c.703_709dup NP_001394779.1:p.Gln237fs frameshift NM_001407851.1:c.703_709dup NP_001394780.1:p.Gln237fs frameshift NM_001407852.1:c.703_709dup NP_001394781.1:p.Gln237fs frameshift NM_001407853.1:c.631_637dup NP_001394782.1:p.Gln213fs frameshift NM_001407854.1:c.844_850dup NP_001394783.1:p.Gln284fs frameshift NM_001407858.1:c.844_850dup NP_001394787.1:p.Gln284fs frameshift NM_001407859.1:c.844_850dup NP_001394788.1:p.Gln284fs frameshift NM_001407860.1:c.841_847dup NP_001394789.1:p.Gln283fs frameshift NM_001407861.1:c.841_847dup NP_001394790.1:p.Gln283fs frameshift NM_001407862.1:c.643_649dup NP_001394791.1:p.Gln217fs frameshift NM_001407863.1:c.721_727dup NP_001394792.1:p.Gln243fs frameshift NM_001407874.1:c.640_646dup NP_001394803.1:p.Gln216fs frameshift NM_001407875.1:c.640_646dup NP_001394804.1:p.Gln216fs frameshift NM_001407879.1:c.634_640dup NP_001394808.1:p.Gln214fs frameshift NM_001407881.1:c.634_640dup NP_001394810.1:p.Gln214fs frameshift NM_001407882.1:c.634_640dup NP_001394811.1:p.Gln214fs frameshift NM_001407884.1:c.634_640dup NP_001394813.1:p.Gln214fs frameshift NM_001407885.1:c.634_640dup NP_001394814.1:p.Gln214fs frameshift NM_001407886.1:c.634_640dup NP_001394815.1:p.Gln214fs frameshift NM_001407887.1:c.634_640dup NP_001394816.1:p.Gln214fs frameshift NM_001407889.1:c.634_640dup NP_001394818.1:p.Gln214fs frameshift NM_001407894.1:c.631_637dup NP_001394823.1:p.Gln213fs frameshift NM_001407895.1:c.631_637dup NP_001394824.1:p.Gln213fs frameshift NM_001407896.1:c.631_637dup NP_001394825.1:p.Gln213fs frameshift NM_001407897.1:c.631_637dup NP_001394826.1:p.Gln213fs frameshift NM_001407898.1:c.631_637dup NP_001394827.1:p.Gln213fs frameshift NM_001407899.1:c.631_637dup NP_001394828.1:p.Gln213fs frameshift NM_001407900.1:c.634_640dup NP_001394829.1:p.Gln214fs frameshift NM_001407902.1:c.634_640dup NP_001394831.1:p.Gln214fs frameshift NM_001407904.1:c.634_640dup NP_001394833.1:p.Gln214fs frameshift NM_001407906.1:c.634_640dup NP_001394835.1:p.Gln214fs frameshift NM_001407907.1:c.634_640dup NP_001394836.1:p.Gln214fs frameshift NM_001407908.1:c.634_640dup NP_001394837.1:p.Gln214fs frameshift NM_001407909.1:c.634_640dup NP_001394838.1:p.Gln214fs frameshift NM_001407910.1:c.634_640dup NP_001394839.1:p.Gln214fs frameshift NM_001407915.1:c.631_637dup NP_001394844.1:p.Gln213fs frameshift NM_001407916.1:c.631_637dup NP_001394845.1:p.Gln213fs frameshift NM_001407917.1:c.631_637dup NP_001394846.1:p.Gln213fs frameshift NM_001407918.1:c.631_637dup NP_001394847.1:p.Gln213fs frameshift NM_001407919.1:c.721_727dup NP_001394848.1:p.Gln243fs frameshift NM_001407920.1:c.580_586dup NP_001394849.1:p.Gln196fs frameshift NM_001407921.1:c.580_586dup NP_001394850.1:p.Gln196fs frameshift NM_001407922.1:c.580_586dup NP_001394851.1:p.Gln196fs frameshift NM_001407923.1:c.580_586dup NP_001394852.1:p.Gln196fs frameshift NM_001407924.1:c.580_586dup NP_001394853.1:p.Gln196fs frameshift NM_001407925.1:c.580_586dup NP_001394854.1:p.Gln196fs frameshift NM_001407926.1:c.580_586dup NP_001394855.1:p.Gln196fs frameshift NM_001407927.1:c.580_586dup NP_001394856.1:p.Gln196fs frameshift NM_001407928.1:c.580_586dup NP_001394857.1:p.Gln196fs frameshift NM_001407929.1:c.580_586dup NP_001394858.1:p.Gln196fs frameshift NM_001407930.1:c.577_583dup NP_001394859.1:p.Gln195fs frameshift NM_001407931.1:c.577_583dup NP_001394860.1:p.Gln195fs frameshift NM_001407932.1:c.577_583dup NP_001394861.1:p.Gln195fs frameshift NM_001407933.1:c.580_586dup NP_001394862.1:p.Gln196fs frameshift NM_001407934.1:c.577_583dup NP_001394863.1:p.Gln195fs frameshift NM_001407935.1:c.580_586dup NP_001394864.1:p.Gln196fs frameshift NM_001407936.1:c.577_583dup NP_001394865.1:p.Gln195fs frameshift NM_001407937.1:c.721_727dup NP_001394866.1:p.Gln243fs frameshift NM_001407938.1:c.721_727dup NP_001394867.1:p.Gln243fs frameshift NM_001407939.1:c.721_727dup NP_001394868.1:p.Gln243fs frameshift NM_001407940.1:c.718_724dup NP_001394869.1:p.Gln242fs frameshift NM_001407941.1:c.718_724dup NP_001394870.1:p.Gln242fs frameshift NM_001407942.1:c.703_709dup NP_001394871.1:p.Gln237fs frameshift NM_001407943.1:c.700_706dup NP_001394872.1:p.Gln236fs frameshift NM_001407944.1:c.703_709dup NP_001394873.1:p.Gln237fs frameshift NM_001407945.1:c.703_709dup NP_001394874.1:p.Gln237fs frameshift NM_001407946.1:c.511_517dup NP_001394875.1:p.Gln173fs frameshift NM_001407947.1:c.511_517dup NP_001394876.1:p.Gln173fs frameshift NM_001407948.1:c.511_517dup NP_001394877.1:p.Gln173fs frameshift NM_001407949.1:c.511_517dup NP_001394878.1:p.Gln173fs frameshift NM_001407950.1:c.511_517dup NP_001394879.1:p.Gln173fs frameshift NM_001407951.1:c.511_517dup NP_001394880.1:p.Gln173fs frameshift NM_001407952.1:c.511_517dup NP_001394881.1:p.Gln173fs frameshift NM_001407953.1:c.511_517dup NP_001394882.1:p.Gln173fs frameshift NM_001407954.1:c.508_514dup NP_001394883.1:p.Gln172fs frameshift NM_001407955.1:c.508_514dup NP_001394884.1:p.Gln172fs frameshift NM_001407956.1:c.508_514dup NP_001394885.1:p.Gln172fs frameshift NM_001407957.1:c.511_517dup NP_001394886.1:p.Gln173fs frameshift NM_001407958.1:c.508_514dup NP_001394887.1:p.Gln172fs frameshift NM_001407959.1:c.463_469dup NP_001394888.1:p.Gln157fs frameshift NM_001407960.1:c.463_469dup NP_001394889.1:p.Gln157fs frameshift NM_001407962.1:c.460_466dup NP_001394891.1:p.Gln156fs frameshift NM_001407963.1:c.463_469dup NP_001394892.1:p.Gln157fs frameshift NM_001407964.1:c.700_706dup NP_001394893.1:p.Gln236fs frameshift NM_001407965.1:c.340_346dup NP_001394894.1:p.Gln116fs frameshift NM_001407966.1:c.-45_-39dup 5 prime UTR NM_001407967.1:c.-45_-39dup 5 prime UTR NM_001407968.1:c.787+57_787+63dup intron variant NM_001407969.1:c.787+57_787+63dup intron variant NM_001407970.1:c.787+57_787+63dup intron variant NM_001407971.1:c.787+57_787+63dup intron variant NM_001407972.1:c.784+57_784+63dup intron variant NM_001407973.1:c.787+57_787+63dup intron variant NM_001407974.1:c.787+57_787+63dup intron variant NM_001407975.1:c.787+57_787+63dup intron variant NM_001407976.1:c.787+57_787+63dup intron variant NM_001407977.1:c.787+57_787+63dup intron variant NM_001407978.1:c.787+57_787+63dup intron variant NM_001407979.1:c.787+57_787+63dup intron variant NM_001407980.1:c.787+57_787+63dup intron variant NM_001407981.1:c.787+57_787+63dup intron variant NM_001407982.1:c.787+57_787+63dup intron variant NM_001407983.1:c.787+57_787+63dup intron variant NM_001407984.1:c.784+57_784+63dup intron variant NM_001407985.1:c.784+57_784+63dup intron variant NM_001407986.1:c.784+57_784+63dup intron variant NM_001407990.1:c.787+57_787+63dup intron variant NM_001407991.1:c.784+57_784+63dup intron variant NM_001407992.1:c.784+57_784+63dup intron variant NM_001407993.1:c.787+57_787+63dup intron variant NM_001408392.1:c.784+57_784+63dup intron variant NM_001408396.1:c.784+57_784+63dup intron variant NM_001408397.1:c.784+57_784+63dup intron variant NM_001408398.1:c.784+57_784+63dup intron variant NM_001408399.1:c.784+57_784+63dup intron variant NM_001408400.1:c.784+57_784+63dup intron variant NM_001408401.1:c.784+57_784+63dup intron variant NM_001408402.1:c.784+57_784+63dup intron variant NM_001408403.1:c.787+57_787+63dup intron variant NM_001408404.1:c.787+57_787+63dup intron variant NM_001408406.1:c.790+54_790+60dup intron variant NM_001408407.1:c.784+57_784+63dup intron variant NM_001408408.1:c.778+57_778+63dup intron variant NM_001408409.1:c.709+57_709+63dup intron variant NM_001408410.1:c.646+57_646+63dup intron variant NM_001408411.1:c.709+57_709+63dup intron variant NM_001408412.1:c.709+57_709+63dup intron variant NM_001408413.1:c.706+57_706+63dup intron variant NM_001408414.1:c.709+57_709+63dup intron variant NM_001408415.1:c.709+57_709+63dup intron variant NM_001408416.1:c.706+57_706+63dup intron variant NM_001408418.1:c.670+1159_670+1165dup intron variant NM_001408419.1:c.670+1159_670+1165dup intron variant NM_001408420.1:c.670+1159_670+1165dup intron variant NM_001408421.1:c.667+1159_667+1165dup intron variant NM_001408422.1:c.670+1159_670+1165dup intron variant NM_001408423.1:c.670+1159_670+1165dup intron variant NM_001408424.1:c.667+1159_667+1165dup intron variant NM_001408425.1:c.664+57_664+63dup intron variant NM_001408426.1:c.664+57_664+63dup intron variant NM_001408427.1:c.664+57_664+63dup intron variant NM_001408428.1:c.664+57_664+63dup intron variant NM_001408429.1:c.664+57_664+63dup intron variant NM_001408430.1:c.664+57_664+63dup intron variant NM_001408431.1:c.667+1159_667+1165dup intron variant NM_001408432.1:c.661+57_661+63dup intron variant NM_001408433.1:c.661+57_661+63dup intron variant NM_001408434.1:c.661+57_661+63dup intron variant NM_001408435.1:c.661+57_661+63dup intron variant NM_001408436.1:c.664+57_664+63dup intron variant NM_001408437.1:c.664+57_664+63dup intron variant NM_001408438.1:c.664+57_664+63dup intron variant NM_001408439.1:c.664+57_664+63dup intron variant NM_001408440.1:c.664+57_664+63dup intron variant NM_001408441.1:c.664+57_664+63dup intron variant NM_001408442.1:c.664+57_664+63dup intron variant NM_001408443.1:c.664+57_664+63dup intron variant NM_001408444.1:c.664+57_664+63dup intron variant NM_001408445.1:c.661+57_661+63dup intron variant NM_001408446.1:c.661+57_661+63dup intron variant NM_001408447.1:c.661+57_661+63dup intron variant NM_001408448.1:c.661+57_661+63dup intron variant NM_001408450.1:c.661+57_661+63dup intron variant NM_001408451.1:c.652+57_652+63dup intron variant NM_001408452.1:c.646+57_646+63dup intron variant NM_001408453.1:c.646+57_646+63dup intron variant NM_001408454.1:c.646+57_646+63dup intron variant NM_001408455.1:c.646+57_646+63dup intron variant NM_001408456.1:c.646+57_646+63dup intron variant NM_001408457.1:c.646+57_646+63dup intron variant NM_001408458.1:c.646+57_646+63dup intron variant NM_001408459.1:c.646+57_646+63dup intron variant NM_001408460.1:c.646+57_646+63dup intron variant NM_001408461.1:c.646+57_646+63dup intron variant NM_001408462.1:c.643+57_643+63dup intron variant NM_001408463.1:c.643+57_643+63dup intron variant NM_001408464.1:c.643+57_643+63dup intron variant NM_001408465.1:c.643+57_643+63dup intron variant NM_001408466.1:c.646+57_646+63dup intron variant NM_001408467.1:c.646+57_646+63dup intron variant NM_001408468.1:c.643+57_643+63dup intron variant NM_001408469.1:c.646+57_646+63dup intron variant NM_001408470.1:c.643+57_643+63dup intron variant NM_001408472.1:c.787+57_787+63dup intron variant NM_001408473.1:c.784+57_784+63dup intron variant NM_001408474.1:c.586+57_586+63dup intron variant NM_001408475.1:c.583+57_583+63dup intron variant NM_001408476.1:c.586+57_586+63dup intron variant NM_001408478.1:c.577+57_577+63dup intron variant NM_001408479.1:c.577+57_577+63dup intron variant NM_001408480.1:c.577+57_577+63dup intron variant NM_001408481.1:c.577+57_577+63dup intron variant NM_001408482.1:c.577+57_577+63dup intron variant NM_001408483.1:c.577+57_577+63dup intron variant NM_001408484.1:c.577+57_577+63dup intron variant NM_001408485.1:c.577+57_577+63dup intron variant NM_001408489.1:c.577+57_577+63dup intron variant NM_001408490.1:c.574+57_574+63dup intron variant NM_001408491.1:c.574+57_574+63dup intron variant NM_001408492.1:c.577+57_577+63dup intron variant NM_001408493.1:c.574+57_574+63dup intron variant NM_001408494.1:c.548-3655_548-3649dup intron variant NM_001408495.1:c.545-3655_545-3649dup intron variant NM_001408496.1:c.523+57_523+63dup intron variant NM_001408497.1:c.523+57_523+63dup intron variant NM_001408498.1:c.523+57_523+63dup intron variant NM_001408499.1:c.523+57_523+63dup intron variant NM_001408500.1:c.523+57_523+63dup intron variant NM_001408501.1:c.523+57_523+63dup intron variant NM_001408502.1:c.454+57_454+63dup intron variant NM_001408503.1:c.520+57_520+63dup intron variant NM_001408504.1:c.520+57_520+63dup intron variant NM_001408505.1:c.520+57_520+63dup intron variant NM_001408506.1:c.460+1159_460+1165dup intron variant NM_001408507.1:c.460+1159_460+1165dup intron variant NM_001408508.1:c.451+57_451+63dup intron variant NM_001408509.1:c.451+57_451+63dup intron variant NM_001408510.1:c.406+57_406+63dup intron variant NM_001408511.1:c.404-3655_404-3649dup intron variant NM_001408512.1:c.283+57_283+63dup intron variant NM_001408513.1:c.577+57_577+63dup intron variant NM_001408514.1:c.577+57_577+63dup intron variant NM_007294.3:c.844_850dupTCATTAC frameshift NM_007297.4:c.703_709dup NP_009228.2:p.Gln237fs frameshift NM_007298.4:c.787+57_787+63dup intron variant NM_007299.4:c.787+57_787+63dup intron variant NM_007300.4:c.844_850dup NP_009231.2:p.Gln284fs frameshift NR_027676.1:n.979_985dup NC_000017.11:g.43094682_43094688dup NC_000017.10:g.41246699_41246705dup NG_005905.2:g.123297_123303dup LRG_292:g.123297_123303dup LRG_292t1:c.843_849dup LRG_292p1:p.Gln284Leufs U14680.1:n.969_970insTCATTAC - Protein change
- Q237fs, Q284fs, Q156fs, Q172fs, Q242fs, Q243fs, Q257fs, Q281fs, Q213fs, Q214fs, Q217fs, Q258fs, Q116fs, Q195fs, Q216fs, Q236fs, Q157fs, Q173fs, Q196fs, Q283fs
- Other names
-
969ins7
- Canonical SPDI
- NC_000017.11:43094680:GTAATGAG:GTAATGAGTAATGAG
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
- -
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
- -
- Links
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
|---|---|---|---|---|---|---|
| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
| BRCA1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
13041 | 14847 | |
Conditions - Germline
| Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Pathogenic (5) |
reviewed by expert panel
|
Oct 18, 2016 | RCV000112803.17 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Aug 10, 2015 | RCV000414853.10 | |
| Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
|
Nov 2, 2020 | RCV000505835.11 | |
| Pathogenic (4) |
criteria provided, multiple submitters, no conflicts
|
Aug 12, 2024 | RCV000496599.18 | |
| Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
Jun 30, 2023 | RCV000165711.15 |
Submissions - Germline
| Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|
|---|---|---|---|---|---|
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Pathogenic
(Oct 18, 2016)
|
reviewed by expert panel
Method: curation
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
germline
|
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)
Accession: SCV000323920.2
First in ClinVar: Apr 04, 2014 Last updated: Feb 07, 2023 |
Comment:
Variant allele predicted to encode a truncated non-functional protein.
|
|
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Pathogenic
(Aug 10, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
Rhabdomyosarcoma
Affected status: yes
Allele origin:
unknown
|
Centre for Mendelian Genomics, University Medical Centre Ljubljana
Accession: SCV000492787.1
First in ClinVar: Jan 13, 2017 Last updated: Jan 13, 2017 |
|
|
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Pathogenic
(Oct 02, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
germline
|
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge
Accession: SCV000326443.4
First in ClinVar: Nov 05, 2016 Last updated: Dec 11, 2022 |
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Pathogenic
(Dec 09, 2022)
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criteria provided, single submitter
Method: research
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: no
Allele origin:
germline
|
Centre for Mendelian Genomics, University Medical Centre Ljubljana
Accession: SCV002762795.2
First in ClinVar: Dec 17, 2022 Last updated: Feb 25, 2023 |
Comment:
PVS1, PS4_STR, PM2_SUP
|
|
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Pathogenic
(Aug 04, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
|
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV004848003.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024 |
Comment:
The p.Gln284fs variant in BRCA1 has been reported in >10 Caucasian individuals with BRCA1-associated cancers (Ozcelik 2003, Stegel 2011, Krajc 2014) and was absent from … (more)
The p.Gln284fs variant in BRCA1 has been reported in >10 Caucasian individuals with BRCA1-associated cancers (Ozcelik 2003, Stegel 2011, Krajc 2014) and was absent from large population studies, though the ability of these studies to accurately detect indels may be limited. This variant is predicted to cause a frameshift, which alters the protein's amino acid sequence beginning at position 284 and leads to a premature stop codon 5 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Heterozygous loss of function of the BRCA1 gene is an established disease mechanism for hereditary breast and ovarian cancer (HBOC). In summary, this variant meets our criteria to be classified as pathogenic for autosomal dominant HBOC. (less)
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Pathogenic
(Oct 30, 2020)
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criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000216452.6
First in ClinVar: Mar 24, 2015 Last updated: May 01, 2024 |
Comment:
The c.844_850dupTCATTAC pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from a duplication of TCATTAC at nucleotide position 844, causing a … (more)
The c.844_850dupTCATTAC pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from a duplication of TCATTAC at nucleotide position 844, causing a translational frameshift with a predicted alternate stop codon (p.Q284Lfs*5). This mutation has been reported in several high-risk breast/ovarian cancer families (Ozcelik H, J. Med. Genet. 2003 Aug; 40(8):e91; Stegel V et al. BMC Med Genet, 2011 Jan;12:9; Novakovi S et al. Int J Oncol, 2012 Nov;41:1619-27; Dobrii J et al. J Hum Genet, 2013 Aug;58:501-7; Krajc M et al. Clin Genet, 2014 Jan;85:59-63; Minucci A et al. Expert Rev Mol Diagn, 2015 Aug;15:1383-403; Cini G et al. BMC Med Genet, 2016 Feb;17:11; Cvelbar M et al. Radiol Oncol, 2017 Jun;51:187-194; Gornjec A et al. BMC Cancer, 2019 Apr;19:296; Nguyen-Dumont T et al. Genet Res (Camb), 2020 08;102:e6) as well as in a pancreatic cancer cohort (Holter S et al. J Clin Oncol, 2015 Oct;33:3124-9). In particular, this mutation has been reported frequently in the Slovenian population (Stegel V et al. BMC Med Genet, 2011 Jan;12:9; Novakovi S et al. Int J Oncol, 2012 Nov;41:1619-27; Krajc M et al. Clin Genet, 2014 Jan;85:59-63). Of note, this alteration is also referred to as 969ins7, 970ins7 , and 850_851insTCATTAC in the literature. In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. (less)
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Pathogenic
(Aug 12, 2024)
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criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV005380637.1
First in ClinVar: Oct 26, 2024 Last updated: Oct 26, 2024 |
Comment:
Variant summary: BRCA1 c.844_850dupTCATTAC (p.Gln284LeufsX5) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein … (more)
Variant summary: BRCA1 c.844_850dupTCATTAC (p.Gln284LeufsX5) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 251110 control chromosomes. c.844_850dupTCATTAC has been reported in the literature in multiple individuals affected with Hereditary Breast And Ovarian Cancer Syndrome (e.g. Stegel_2011, Ozcelik_2003, Krajc_2014, van der Stoep_2009). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 21232165, 12920083, 23397983, 19370767). ClinVar contains an entry for this variant (Variation ID: 55735). Based on the evidence outlined above, the variant was classified as pathogenic. (less)
|
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Pathogenic
(Oct 30, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000779139.2
First in ClinVar: Sep 28, 2017 Last updated: Sep 28, 2017 |
Comment:
This duplication of seven nucleotides in BRCA1 is denoted c.844_850dupTCATTAC at the cDNA level and p.Gln284LeufsX5 (Q284LfsX5) at the protein level. The normal sequence, with … (more)
This duplication of seven nucleotides in BRCA1 is denoted c.844_850dupTCATTAC at the cDNA level and p.Gln284LeufsX5 (Q284LfsX5) at the protein level. The normal sequence, with the bases that are duplicated in brackets, is CAGC[dupTCATTAC]AGCA. The duplication causes a frameshift which changes a Glutamine to a Leucine at codon 284, and creates a premature stop codon at position 5 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. BRCA1 c.844_850dupTCATTAC, previously published as 969ins7 using alternate nomenclature, has been reported in multiple individuals with hereditary breast and/or ovarian cancer and is described as a recurrent variant in the Slovenian population (Stegel 2011, Navokovic 2012, Dobricic 2013, Karami 2013, Cini 2016, Cvelbar 2017). We consider this variant to be pathogenic. (less)
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Pathogenic
(Apr 02, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
Department of Molecular Diagnostics, Institute of Oncology Ljubljana
Accession: SCV001499626.1
First in ClinVar: Mar 07, 2021 Last updated: Mar 07, 2021 |
|
|
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Pathogenic
(Nov 02, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
unknown
|
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000296400.3
First in ClinVar: Apr 04, 2014 Last updated: Jan 03, 2022 |
Comment:
This frameshift variant causes the premature termination of BRCA1 protein synthesis. In addition, it has been reported in individuals with breast, ovarian, and pancreatic cancers … (more)
This frameshift variant causes the premature termination of BRCA1 protein synthesis. In addition, it has been reported in individuals with breast, ovarian, and pancreatic cancers in the published literature (PMID: 30940100 (2019), 26306726 (2015), 25940717 (2015), 23635950 (2013), 12920083 (2003)). This variant has not been reported in large, multi-ethnic general populations. Therefore, the variant is classified as pathogenic. (less)
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Pathogenic
(Nov 17, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001591510.4
First in ClinVar: May 10, 2021 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Gln284Leufs*5) in the BRCA1 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Gln284Leufs*5) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 55735). This premature translational stop signal has been observed in individual(s) with pancreatic ductal adenocarcinoma and a personal and/or family history of breast and/or ovarian cancer (PMID: 12920083, 16287141, 22923021, 23635950, 25940717, 26306726, 28740454). This variant is not present in population databases (gnomAD no frequency). (less)
|
|
|
Pathogenic
(Jun 30, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV001736476.3
First in ClinVar: Jun 19, 2021 Last updated: Feb 14, 2024 |
Comment:
This variant inserts 7 nucleotides in exon 10 of the BRCA1 gene, creating a frameshift and premature translation stop signal. This variant is also known … (more)
This variant inserts 7 nucleotides in exon 10 of the BRCA1 gene, creating a frameshift and premature translation stop signal. This variant is also known as 969ins7 and 970ins7 in the literature. This variant is expected to result in an absent or non-functional protein product. To our knowledge, functional studies have not been reported for this variant. This variant has been detected in multiple individuals and families affected with breast and/or ovarian cancer (PMID: 12920083, 23635950, 26852130) including recurrent affected families in Slovenia (PMID: 22923021). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. (less)
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Pathogenic
(Jan 31, 2014)
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no assertion criteria provided
Method: research
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Hereditary breast ovarian cancer syndrome
Affected status: yes
Allele origin:
germline
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Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000587081.1 First in ClinVar: Aug 07, 2017 Last updated: Aug 07, 2017 |
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Uncertain significance
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
unknown
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Department of Pathology and Laboratory Medicine, Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV001552030.1 First in ClinVar: Apr 13, 2021 Last updated: Apr 13, 2021 |
Number of individuals with the variant: 1
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Pathogenic
(Nov 17, 1998)
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no assertion criteria provided
Method: clinical testing
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Breast-ovarian cancer, familial 1
Affected status: yes
Allele origin:
germline
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Breast Cancer Information Core (BIC) (BRCA1)
Accession: SCV000145704.1
First in ClinVar: Apr 04, 2014 Last updated: Apr 04, 2014 |
Observation 1:
Number of individuals with the variant: 1
Ethnicity/Population group: Caucasian
Geographic origin: Austria
Observation 2:
Number of individuals with the variant: 1
Ethnicity/Population group: Caucasian
Geographic origin: Germany
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Comment:
Comment:
PVS1, PS4_STR, PM2_SUP
Comment:
The p.Gln284fs variant in BRCA1 has been reported in >10 Caucasian individuals with BRCA1-associated cancers (Ozcelik 2003, Stegel 2011, Krajc 2014) and was absent from large population studies, though the ability of these studies to accurately detect indels may be limited. This variant is predicted to cause a frameshift, which alters the protein's amino acid sequence beginning at position 284 and leads to a premature stop codon 5 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Heterozygous loss of function of the BRCA1 gene is an established disease mechanism for hereditary breast and ovarian cancer (HBOC). In summary, this variant meets our criteria to be classified as pathogenic for autosomal dominant HBOC.
Comment:
The c.844_850dupTCATTAC pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from a duplication of TCATTAC at nucleotide position 844, causing a translational frameshift with a predicted alternate stop codon (p.Q284Lfs*5). This mutation has been reported in several high-risk breast/ovarian cancer families (Ozcelik H, J. Med. Genet. 2003 Aug; 40(8):e91; Stegel V et al. BMC Med Genet, 2011 Jan;12:9; Novakovi S et al. Int J Oncol, 2012 Nov;41:1619-27; Dobrii J et al. J Hum Genet, 2013 Aug;58:501-7; Krajc M et al. Clin Genet, 2014 Jan;85:59-63; Minucci A et al. Expert Rev Mol Diagn, 2015 Aug;15:1383-403; Cini G et al. BMC Med Genet, 2016 Feb;17:11; Cvelbar M et al. Radiol Oncol, 2017 Jun;51:187-194; Gornjec A et al. BMC Cancer, 2019 Apr;19:296; Nguyen-Dumont T et al. Genet Res (Camb), 2020 08;102:e6) as well as in a pancreatic cancer cohort (Holter S et al. J Clin Oncol, 2015 Oct;33:3124-9). In particular, this mutation has been reported frequently in the Slovenian population (Stegel V et al. BMC Med Genet, 2011 Jan;12:9; Novakovi S et al. Int J Oncol, 2012 Nov;41:1619-27; Krajc M et al. Clin Genet, 2014 Jan;85:59-63). Of note, this alteration is also referred to as 969ins7, 970ins7 , and 850_851insTCATTAC in the literature. In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Comment:
Variant summary: BRCA1 c.844_850dupTCATTAC (p.Gln284LeufsX5) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 251110 control chromosomes. c.844_850dupTCATTAC has been reported in the literature in multiple individuals affected with Hereditary Breast And Ovarian Cancer Syndrome (e.g. Stegel_2011, Ozcelik_2003, Krajc_2014, van der Stoep_2009). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 21232165, 12920083, 23397983, 19370767). ClinVar contains an entry for this variant (Variation ID: 55735). Based on the evidence outlined above, the variant was classified as pathogenic.
Comment:
This duplication of seven nucleotides in BRCA1 is denoted c.844_850dupTCATTAC at the cDNA level and p.Gln284LeufsX5 (Q284LfsX5) at the protein level. The normal sequence, with the bases that are duplicated in brackets, is CAGC[dupTCATTAC]AGCA. The duplication causes a frameshift which changes a Glutamine to a Leucine at codon 284, and creates a premature stop codon at position 5 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. BRCA1 c.844_850dupTCATTAC, previously published as 969ins7 using alternate nomenclature, has been reported in multiple individuals with hereditary breast and/or ovarian cancer and is described as a recurrent variant in the Slovenian population (Stegel 2011, Navokovic 2012, Dobricic 2013, Karami 2013, Cini 2016, Cvelbar 2017). We consider this variant to be pathogenic.
Comment:
This frameshift variant causes the premature termination of BRCA1 protein synthesis. In addition, it has been reported in individuals with breast, ovarian, and pancreatic cancers in the published literature (PMID: 30940100 (2019), 26306726 (2015), 25940717 (2015), 23635950 (2013), 12920083 (2003)). This variant has not been reported in large, multi-ethnic general populations. Therefore, the variant is classified as pathogenic.
Comment:
This sequence change creates a premature translational stop signal (p.Gln284Leufs*5) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 55735). This premature translational stop signal has been observed in individual(s) with pancreatic ductal adenocarcinoma and a personal and/or family history of breast and/or ovarian cancer (PMID: 12920083, 16287141, 22923021, 23635950, 25940717, 26306726, 28740454). This variant is not present in population databases (gnomAD no frequency).
Comment:
This variant inserts 7 nucleotides in exon 10 of the BRCA1 gene, creating a frameshift and premature translation stop signal. This variant is also known as 969ins7 and 970ins7 in the literature. This variant is expected to result in an absent or non-functional protein product. To our knowledge, functional studies have not been reported for this variant. This variant has been detected in multiple individuals and families affected with breast and/or ovarian cancer (PMID: 12920083, 23635950, 26852130) including recurrent affected families in Slovenia (PMID: 22923021). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Germline Functional Evidence
| There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Comment:
Variant allele predicted to encode a truncated non-functional protein.
Comment:
PVS1, PS4_STR, PM2_SUP
Comment:
The p.Gln284fs variant in BRCA1 has been reported in >10 Caucasian individuals with BRCA1-associated cancers (Ozcelik 2003, Stegel 2011, Krajc 2014) and was absent from large population studies, though the ability of these studies to accurately detect indels may be limited. This variant is predicted to cause a frameshift, which alters the protein's amino acid sequence beginning at position 284 and leads to a premature stop codon 5 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Heterozygous loss of function of the BRCA1 gene is an established disease mechanism for hereditary breast and ovarian cancer (HBOC). In summary, this variant meets our criteria to be classified as pathogenic for autosomal dominant HBOC.
Comment:
The c.844_850dupTCATTAC pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from a duplication of TCATTAC at nucleotide position 844, causing a translational frameshift with a predicted alternate stop codon (p.Q284Lfs*5). This mutation has been reported in several high-risk breast/ovarian cancer families (Ozcelik H, J. Med. Genet. 2003 Aug; 40(8):e91; Stegel V et al. BMC Med Genet, 2011 Jan;12:9; Novakovi S et al. Int J Oncol, 2012 Nov;41:1619-27; Dobrii J et al. J Hum Genet, 2013 Aug;58:501-7; Krajc M et al. Clin Genet, 2014 Jan;85:59-63; Minucci A et al. Expert Rev Mol Diagn, 2015 Aug;15:1383-403; Cini G et al. BMC Med Genet, 2016 Feb;17:11; Cvelbar M et al. Radiol Oncol, 2017 Jun;51:187-194; Gornjec A et al. BMC Cancer, 2019 Apr;19:296; Nguyen-Dumont T et al. Genet Res (Camb), 2020 08;102:e6) as well as in a pancreatic cancer cohort (Holter S et al. J Clin Oncol, 2015 Oct;33:3124-9). In particular, this mutation has been reported frequently in the Slovenian population (Stegel V et al. BMC Med Genet, 2011 Jan;12:9; Novakovi S et al. Int J Oncol, 2012 Nov;41:1619-27; Krajc M et al. Clin Genet, 2014 Jan;85:59-63). Of note, this alteration is also referred to as 969ins7, 970ins7 , and 850_851insTCATTAC in the literature. In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Comment:
Variant summary: BRCA1 c.844_850dupTCATTAC (p.Gln284LeufsX5) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 251110 control chromosomes. c.844_850dupTCATTAC has been reported in the literature in multiple individuals affected with Hereditary Breast And Ovarian Cancer Syndrome (e.g. Stegel_2011, Ozcelik_2003, Krajc_2014, van der Stoep_2009). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 21232165, 12920083, 23397983, 19370767). ClinVar contains an entry for this variant (Variation ID: 55735). Based on the evidence outlined above, the variant was classified as pathogenic.
Comment:
This duplication of seven nucleotides in BRCA1 is denoted c.844_850dupTCATTAC at the cDNA level and p.Gln284LeufsX5 (Q284LfsX5) at the protein level. The normal sequence, with the bases that are duplicated in brackets, is CAGC[dupTCATTAC]AGCA. The duplication causes a frameshift which changes a Glutamine to a Leucine at codon 284, and creates a premature stop codon at position 5 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. BRCA1 c.844_850dupTCATTAC, previously published as 969ins7 using alternate nomenclature, has been reported in multiple individuals with hereditary breast and/or ovarian cancer and is described as a recurrent variant in the Slovenian population (Stegel 2011, Navokovic 2012, Dobricic 2013, Karami 2013, Cini 2016, Cvelbar 2017). We consider this variant to be pathogenic.
Comment:
This frameshift variant causes the premature termination of BRCA1 protein synthesis. In addition, it has been reported in individuals with breast, ovarian, and pancreatic cancers in the published literature (PMID: 30940100 (2019), 26306726 (2015), 25940717 (2015), 23635950 (2013), 12920083 (2003)). This variant has not been reported in large, multi-ethnic general populations. Therefore, the variant is classified as pathogenic.
Comment:
This sequence change creates a premature translational stop signal (p.Gln284Leufs*5) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 55735). This premature translational stop signal has been observed in individual(s) with pancreatic ductal adenocarcinoma and a personal and/or family history of breast and/or ovarian cancer (PMID: 12920083, 16287141, 22923021, 23635950, 25940717, 26306726, 28740454). This variant is not present in population databases (gnomAD no frequency).
Comment:
This variant inserts 7 nucleotides in exon 10 of the BRCA1 gene, creating a frameshift and premature translation stop signal. This variant is also known as 969ins7 and 970ins7 in the literature. This variant is expected to result in an absent or non-functional protein product. To our knowledge, functional studies have not been reported for this variant. This variant has been detected in multiple individuals and families affected with breast and/or ovarian cancer (PMID: 12920083, 23635950, 26852130) including recurrent affected families in Slovenia (PMID: 22923021). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Genetic testing in Poland and Ukraine: should comprehensive germline testing of BRCA1 and BRCA2 be recommended for women with breast and ovarian cancer? | Nguyen-Dumont T | Genetics research | 2020 | PMID: 32772980 |
| Cytology material is equivalent to tumor tissue in determining mutations of BRCA 1/2 genes in patients with tubo-ovarian high grade serous carcinoma. | Gornjec A | BMC cancer | 2019 | PMID: 30940100 |
| Genetic Counselling, BRCA1/2 Status and Clinico-pathologic Characteristics of Patients with Ovarian Cancer before 50 Years of Age. | Cvelbar M | Radiology and oncology | 2017 | PMID: 28740454 |
| Tracking of the origin of recurrent mutations of the BRCA1 and BRCA2 genes in the North-East of Italy and improved mutation analysis strategy. | Cini G | BMC medical genetics | 2016 | PMID: 26852130 |
| Clinical impact on ovarian cancer patients of massive parallel sequencing for BRCA mutation detection: the experience at Gemelli hospital and a literature review. | Minucci A | Expert review of molecular diagnostics | 2015 | PMID: 26306726 |
| Germline BRCA Mutations in a Large Clinic-Based Cohort of Patients With Pancreatic Adenocarcinoma. | Holter S | Journal of clinical oncology : official journal of the American Society of Clinical Oncology | 2015 | PMID: 25940717 |
| Geographical distribution of Slovenian BRCA1/2 families according to family origin: implications for genetic screening. | Krajc M | Clinical genetics | 2014 | PMID: 23397983 |
| Serbian high-risk families: extensive results on BRCA mutation spectra and frequency. | Dobričić J | Journal of human genetics | 2013 | PMID: 23635950 |
| Novel BRCA1 and BRCA2 pathogenic mutations in Slovene hereditary breast and ovarian cancer families. | Novaković S | International journal of oncology | 2012 | PMID: 22923021 |
| The occurrence of germline BRCA1 and BRCA2 sequence alterations in Slovenian population. | Stegel V | BMC medical genetics | 2011 | PMID: 21232165 |
| Characterization of BRCA1 and BRCA2 deleterious mutations and variants of unknown clinical significance in unilateral and bilateral breast cancer: the WECARE study. | Borg A | Human mutation | 2010 | PMID: 20104584 |
| Diagnostic guidelines for high-resolution melting curve (HRM) analysis: an interlaboratory validation of BRCA1 mutation scanning using the 96-well LightScanner. | van der Stoep N | Human mutation | 2009 | PMID: 19370767 |
| Younger birth cohort correlates with higher breast and ovarian cancer risk in European BRCA1 mutation carriers. | Kroiss R | Human mutation | 2005 | PMID: 16287141 |
| Individual and family characteristics associated with protein truncating BRCA1 and BRCA2 mutations in an Ontario population based series from the Cooperative Family Registry for Breast Cancer Studies. | Ozcelik H | Journal of medical genetics | 2003 | PMID: 12920083 |
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Text-mined citations for rs80357989 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Nov 03, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.