ClinVar Genomic variation as it relates to human health
NM_020975.6(RET):c.3022A>T (p.Met1008Leu)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_020975.6(RET):c.3022A>T (p.Met1008Leu)
Variation ID: 486329 Accession: VCV000486329.13
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 10q11.21 10: 43124965 (GRCh38) [ NCBI UCSC ] 10: 43620413 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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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 Jan 1, 2018 May 1, 2024 Feb 29, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_020975.6:c.3022A>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_066124.1:p.Met1008Leu missense NM_000323.2:c.3022A>T NP_000314.1:p.Met1008Leu missense NM_001355216.2:c.2260A>T NP_001342145.1:p.Met754Leu missense NM_001406743.1:c.3022A>T NP_001393672.1:p.Met1008Leu missense NM_001406744.1:c.3022A>T NP_001393673.1:p.Met1008Leu missense NM_001406759.1:c.3022A>T NP_001393688.1:p.Met1008Leu missense NM_001406760.1:c.3022A>T NP_001393689.1:p.Met1008Leu missense NM_001406761.1:c.2893A>T NP_001393690.1:p.Met965Leu missense NM_001406762.1:c.2893A>T NP_001393691.1:p.Met965Leu missense NM_001406763.1:c.2887A>T NP_001393692.1:p.Met963Leu missense NM_001406764.1:c.2893A>T NP_001393693.1:p.Met965Leu missense NM_001406765.1:c.2887A>T NP_001393694.1:p.Met963Leu missense NM_001406766.1:c.2734A>T NP_001393695.1:p.Met912Leu missense NM_001406767.1:c.2734A>T NP_001393696.1:p.Met912Leu missense NM_001406768.1:c.2758A>T NP_001393697.1:p.Met920Leu missense NM_001406769.1:c.2626A>T NP_001393698.1:p.Met876Leu missense NM_001406770.1:c.2734A>T NP_001393699.1:p.Met912Leu missense NM_001406771.1:c.2584A>T NP_001393700.1:p.Met862Leu missense NM_001406772.1:c.2626A>T NP_001393701.1:p.Met876Leu missense NM_001406773.1:c.2584A>T NP_001393702.1:p.Met862Leu missense NM_001406774.1:c.2497A>T NP_001393703.1:p.Met833Leu missense NM_001406775.1:c.2296A>T NP_001393704.1:p.Met766Leu missense NM_001406776.1:c.2296A>T NP_001393705.1:p.Met766Leu missense NM_001406777.1:c.2296A>T NP_001393706.1:p.Met766Leu missense NM_001406778.1:c.2296A>T NP_001393707.1:p.Met766Leu missense NM_001406779.1:c.2125A>T NP_001393708.1:p.Met709Leu missense NM_001406780.1:c.2125A>T NP_001393709.1:p.Met709Leu missense NM_001406781.1:c.2125A>T NP_001393710.1:p.Met709Leu missense NM_001406782.1:c.2125A>T NP_001393711.1:p.Met709Leu missense NM_001406783.1:c.1996A>T NP_001393712.1:p.Met666Leu missense NM_001406784.1:c.2032A>T NP_001393713.1:p.Met678Leu missense NM_001406785.1:c.2005A>T NP_001393714.1:p.Met669Leu missense NM_001406786.1:c.1996A>T NP_001393715.1:p.Met666Leu missense NM_001406787.1:c.1990A>T NP_001393716.1:p.Met664Leu missense NM_001406788.1:c.1837A>T NP_001393717.1:p.Met613Leu missense NM_001406789.1:c.1837A>T NP_001393718.1:p.Met613Leu missense NM_001406790.1:c.1837A>T NP_001393719.1:p.Met613Leu missense NM_001406791.1:c.1717A>T NP_001393720.1:p.Met573Leu missense NM_001406792.1:c.1573A>T NP_001393721.1:p.Met525Leu missense NM_001406793.1:c.1573A>T NP_001393722.1:p.Met525Leu missense NM_001406794.1:c.1573A>T NP_001393723.1:p.Met525Leu missense NM_020629.2:c.3022A>T NP_065680.1:p.Met1008Leu missense NM_020630.7:c.3022A>T NP_065681.1:p.Met1008Leu missense NC_000010.11:g.43124965A>T NC_000010.10:g.43620413A>T NG_007489.1:g.52897A>T LRG_518:g.52897A>T LRG_518t1:c.3022A>T LRG_518p1:p.Met1008Leu LRG_518t2:c.3022A>T LRG_518p2:p.Met1008Leu - Protein change
- M1008L, M754L, M525L, M669L, M678L, M912L, M920L, M963L, M965L, M613L, M664L, M666L, M766L, M862L, M573L, M709L, M833L, M876L
- Other names
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- Canonical SPDI
- NC_000010.11:43124964:A:T
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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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.
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Allele frequency
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The frequency of the allele represented by this VCV record.
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Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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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
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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. |
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RET | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
3522 | 3642 |
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
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Uncertain significance (1) |
criteria provided, single submitter
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Feb 29, 2024 | RCV000569684.4 | |
Uncertain significance (1) |
criteria provided, single submitter
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Nov 12, 2021 | RCV000817531.5 | |
Uncertain significance (1) |
criteria provided, single submitter
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Feb 3, 2022 | RCV002483541.1 |
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
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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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Uncertain significance
(Feb 29, 2024)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV000674879.5
First in ClinVar: Jan 01, 2018 Last updated: May 01, 2024 |
Comment:
The p.M1008L variant (also known as c.3022A>T), located in coding exon 18 of the RET gene, results from an A to T substitution at nucleotide … (more)
The p.M1008L variant (also known as c.3022A>T), located in coding exon 18 of the RET gene, results from an A to T substitution at nucleotide position 3022. The methionine at codon 1008 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. (less)
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Uncertain significance
(Feb 03, 2022)
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criteria provided, single submitter
Method: clinical testing
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Hirschsprung disease, susceptibility to, 1
Familial medullary thyroid carcinoma Multiple endocrine neoplasia type 2B Pheochromocytoma Multiple endocrine neoplasia type 2A
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV002779037.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Uncertain significance
(Nov 12, 2021)
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criteria provided, single submitter
Method: clinical testing
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Multiple endocrine neoplasia, type 2
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000958097.5
First in ClinVar: Aug 14, 2019 Last updated: Feb 07, 2023 |
Comment:
This sequence change replaces methionine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1008 of the RET protein (p.Met1008Leu). … (more)
This sequence change replaces methionine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1008 of the RET protein (p.Met1008Leu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RET-related conditions. ClinVar contains an entry for this variant (Variation ID: 486329). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. (less)
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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. |
Citations for germline classification of this variant
HelpThere are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar. |
Text-mined citations for rs1554820077 ...
HelpRecord last updated May 12, 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.