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NM_004369.4(COL6A3):c.5950C>T (p.Arg1984Ter) AND Bethlem myopathy 1A

Germline classification:
Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:
Aug 19, 2022
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV002290033.5

Allele description [Variation Report for NM_004369.4(COL6A3):c.5950C>T (p.Arg1984Ter)]

NM_004369.4(COL6A3):c.5950C>T (p.Arg1984Ter)

Gene:
COL6A3:collagen type VI alpha 3 chain [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2q37.3
Genomic location:
Preferred name:
NM_004369.4(COL6A3):c.5950C>T (p.Arg1984Ter)
HGVS:
  • NC_000002.12:g.237363366G>A
  • NG_008676.1:g.55842C>T
  • NM_004369.4:c.5950C>TMANE SELECT
  • NM_057166.5:c.4129C>T
  • NM_057167.4:c.5332C>T
  • NP_004360.2:p.Arg1984Ter
  • NP_476507.3:p.Arg1377Ter
  • NP_476508.2:p.Arg1778Ter
  • LRG_473:g.55842C>T
  • NC_000002.11:g.238272009G>A
Protein change:
R1377*
Links:
dbSNP: rs771941724
NCBI 1000 Genomes Browser:
rs771941724
Molecular consequence:
  • NM_004369.4:c.5950C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_057166.5:c.4129C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_057167.4:c.5332C>T - nonsense - [Sequence Ontology: SO:0001587]
Observations:
1

Condition(s)

Name:
Bethlem myopathy 1A
Synonyms:
Myopathy, benign congenital, with contractures; Bethlem myopathy 1
Identifiers:
MONDO: MONDO:0024530; MedGen: CN029274; Orphanet: 610; OMIM: 158810

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002581261MGZ Medical Genetics Center
criteria provided, single submitter

(ACMG Guidelines, 2015)		Likely pathogenic
(Aug 19, 2022) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

SCV003265104Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Jun 26, 2022) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyes1not providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Sequential targeted exome sequencing of 1001 patients affected by unexplained limb-girdle weakness.

Töpf A, Johnson K, Bates A, Phillips L, Chao KR, England EM, Laricchia KM, Mullen T, Valkanas E, Xu L, Bertoli M, Blain A, Casasús AB, Duff J, Mroczek M, Specht S, Lek M, Ensini M, MacArthur DG; MYO-SEQ consortium., Straub V.

Genet Med. 2020 Sep;22(9):1478-1488. doi: 10.1038/s41436-020-0840-3. Epub 2020 Jun 11.

PubMed [citation]
PMID:
32528171
PMCID:
PMC7462745
See all PubMed Citations (4)

Details of each submission

From MGZ Medical Genetics Center, SCV002581261.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided1not providednot providednot provided

From Invitae, SCV003265104.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 635081). This premature translational stop signal has been observed in individual(s) with clinical features of COL6A3-related conditions (PMID: 32528171). This variant is present in population databases (rs771941724, gnomAD 0.007%). This sequence change creates a premature translational stop signal (p.Arg1984*) in the COL6A3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in COL6A3 are known to be pathogenic (PMID: 26004199).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: May 12, 2024