ClinVar Genomic variation as it relates to human health
NM_020975.6(RET):c.1811C>T (p.Ala604Val)
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.1811C>T (p.Ala604Val)
Variation ID: 862826 Accession: VCV000862826.10
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 10q11.21 10: 43113607 (GRCh38) [ NCBI UCSC ] 10: 43609055 (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 Apr 15, 2020 Feb 20, 2024 May 10, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_020975.6:c.1811C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_066124.1:p.Ala604Val missense NM_000323.2:c.1811C>T NP_000314.1:p.Ala604Val missense NM_001355216.2:c.1049C>T NP_001342145.1:p.Ala350Val missense NM_001406743.1:c.1811C>T NP_001393672.1:p.Ala604Val missense NM_001406744.1:c.1811C>T NP_001393673.1:p.Ala604Val missense NM_001406759.1:c.1811C>T NP_001393688.1:p.Ala604Val missense NM_001406760.1:c.1811C>T NP_001393689.1:p.Ala604Val missense NM_001406761.1:c.1682C>T NP_001393690.1:p.Ala561Val missense NM_001406762.1:c.1682C>T NP_001393691.1:p.Ala561Val missense NM_001406763.1:c.1811C>T NP_001393692.1:p.Ala604Val missense NM_001406764.1:c.1682C>T NP_001393693.1:p.Ala561Val missense NM_001406765.1:c.1811C>T NP_001393694.1:p.Ala604Val missense NM_001406766.1:c.1523C>T NP_001393695.1:p.Ala508Val missense NM_001406767.1:c.1523C>T NP_001393696.1:p.Ala508Val missense NM_001406768.1:c.1682C>T NP_001393697.1:p.Ala561Val missense NM_001406769.1:c.1415C>T NP_001393698.1:p.Ala472Val missense NM_001406770.1:c.1523C>T NP_001393699.1:p.Ala508Val missense NM_001406771.1:c.1373C>T NP_001393700.1:p.Ala458Val missense NM_001406772.1:c.1415C>T NP_001393701.1:p.Ala472Val missense NM_001406773.1:c.1373C>T NP_001393702.1:p.Ala458Val missense NM_001406774.1:c.1286C>T NP_001393703.1:p.Ala429Val missense NM_001406775.1:c.1085C>T NP_001393704.1:p.Ala362Val missense NM_001406776.1:c.1085C>T NP_001393705.1:p.Ala362Val missense NM_001406777.1:c.1085C>T NP_001393706.1:p.Ala362Val missense NM_001406778.1:c.1085C>T NP_001393707.1:p.Ala362Val missense NM_001406779.1:c.914C>T NP_001393708.1:p.Ala305Val missense NM_001406780.1:c.914C>T NP_001393709.1:p.Ala305Val missense NM_001406781.1:c.914C>T NP_001393710.1:p.Ala305Val missense NM_001406782.1:c.914C>T NP_001393711.1:p.Ala305Val missense NM_001406783.1:c.785C>T NP_001393712.1:p.Ala262Val missense NM_001406784.1:c.821C>T NP_001393713.1:p.Ala274Val missense NM_001406786.1:c.785C>T NP_001393715.1:p.Ala262Val missense NM_001406787.1:c.914C>T NP_001393716.1:p.Ala305Val missense NM_001406788.1:c.626C>T NP_001393717.1:p.Ala209Val missense NM_001406789.1:c.626C>T NP_001393718.1:p.Ala209Val missense NM_001406790.1:c.626C>T NP_001393719.1:p.Ala209Val missense NM_001406792.1:c.362C>T NP_001393721.1:p.Ala121Val missense NM_001406793.1:c.362C>T NP_001393722.1:p.Ala121Val missense NM_001406794.1:c.362C>T NP_001393723.1:p.Ala121Val missense NM_020629.2:c.1811C>T NP_065680.1:p.Ala604Val missense NM_020630.7:c.1811C>T NP_065681.1:p.Ala604Val missense NC_000010.11:g.43113607C>T NC_000010.10:g.43609055C>T NG_007489.1:g.41539C>T LRG_518:g.41539C>T LRG_518t1:c.1811C>T LRG_518p1:p.Ala604Val LRG_518t2:c.1811C>T LRG_518p2:p.Ala604Val - Protein change
- A350V, A604V, A305V, A362V, A458V, A561V, A274V, A472V, A121V, A209V, A262V, A429V, A508V
- Other names
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- Canonical SPDI
- NC_000010.11:43113606:C: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.
Trans-Omics for Precision Medicine (TOPMed) 0.00000
The Genome Aggregation Database (gnomAD) 0.00001
- Links
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
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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 |
3382 | 3500 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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
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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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May 10, 2023 | RCV001069638.7 | |
Uncertain significance (1) |
criteria provided, single submitter
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Dec 29, 2021 | RCV002482131.1 | |
Uncertain significance (1) |
criteria provided, single submitter
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Mar 9, 2023 | RCV003396723.4 |
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
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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
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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
(Dec 29, 2021)
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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: SCV002794185.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Uncertain significance
(Mar 09, 2023)
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criteria provided, single submitter
Method: clinical testing
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RET-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV004112770.1
First in ClinVar: Nov 20, 2023 Last updated: Nov 20, 2023 |
Comment:
The RET c.1811C>T variant is predicted to result in the amino acid substitution p.Ala604Val. To our knowledge, this variant has not been reported in the … (more)
The RET c.1811C>T variant is predicted to result in the amino acid substitution p.Ala604Val. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. It is interpreted as uncertain significance in ClinVar (https://preview.ncbi.nlm.nih.gov/clinvar/variation/862826/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. (less)
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Uncertain significance
(May 10, 2023)
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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: SCV001234819.5
First in ClinVar: Apr 15, 2020 Last updated: Feb 20, 2024 |
Comment:
This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 604 of the RET protein (p.Ala604Val). … (more)
This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 604 of the RET protein (p.Ala604Val). This variant is not present in population databases (gnomAD no frequency). 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant  is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 862826). This variant has not been reported in the literature in individuals affected with RET-related conditions. (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 rs1286776938 ...
HelpRecord last updated Mar 11, 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.