ClinVar Genomic variation as it relates to human health
NM_020975.6(RET):c.1832_1833delinsAT (p.Cys611Tyr)
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.1832_1833delinsAT (p.Cys611Tyr)
Variation ID: 2136858 Accession: VCV002136858.2
- Type and length
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Indel, 2 bp
- Location
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Cytogenetic: 10q11.21 10: 43113628-43113629 (GRCh38) [ NCBI UCSC ] 10: 43609076-43609077 (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 Feb 8, 2023 Feb 14, 2024 Apr 12, 2022 - HGVS
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Nucleotide Protein Molecular
consequenceNM_020975.6:c.1832_1833delinsAT MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_066124.1:p.Cys611Tyr missense NM_000323.2:c.1832_1833delGCinsAT NP_000314.1:p.Cys611Tyr missense NM_001355216.2:c.1070_1071delGCinsAT NP_001342145.1:p.Cys357Tyr missense NM_001406743.1:c.1832_1833delGCinsAT NP_001393672.1:p.Cys611Tyr missense NM_001406744.1:c.1832_1833delGCinsAT NP_001393673.1:p.Cys611Tyr missense NM_001406759.1:c.1832_1833delGCinsAT NP_001393688.1:p.Cys611Tyr missense NM_001406760.1:c.1832_1833delGCinsAT NP_001393689.1:p.Cys611Tyr missense NM_001406761.1:c.1703_1704delGCinsAT NP_001393690.1:p.Cys568Tyr missense NM_001406762.1:c.1703_1704delGCinsAT NP_001393691.1:p.Cys568Tyr missense NM_001406763.1:c.1832_1833delGCinsAT NP_001393692.1:p.Cys611Tyr missense NM_001406764.1:c.1703_1704delGCinsAT NP_001393693.1:p.Cys568Tyr missense NM_001406765.1:c.1832_1833delGCinsAT NP_001393694.1:p.Cys611Tyr missense NM_001406766.1:c.1544_1545delGCinsAT NP_001393695.1:p.Cys515Tyr missense NM_001406767.1:c.1544_1545delGCinsAT NP_001393696.1:p.Cys515Tyr missense NM_001406768.1:c.1703_1704delGCinsAT NP_001393697.1:p.Cys568Tyr missense NM_001406769.1:c.1436_1437delGCinsAT NP_001393698.1:p.Cys479Tyr missense NM_001406770.1:c.1544_1545delGCinsAT NP_001393699.1:p.Cys515Tyr missense NM_001406771.1:c.1394_1395delGCinsAT NP_001393700.1:p.Cys465Tyr missense NM_001406772.1:c.1436_1437delGCinsAT NP_001393701.1:p.Cys479Tyr missense NM_001406773.1:c.1394_1395delGCinsAT NP_001393702.1:p.Cys465Tyr missense NM_001406774.1:c.1307_1308delGCinsAT NP_001393703.1:p.Cys436Tyr missense NM_001406775.1:c.1106_1107delGCinsAT NP_001393704.1:p.Cys369Tyr missense NM_001406776.1:c.1106_1107delGCinsAT NP_001393705.1:p.Cys369Tyr missense NM_001406777.1:c.1106_1107delGCinsAT NP_001393706.1:p.Cys369Tyr missense NM_001406778.1:c.1106_1107delGCinsAT NP_001393707.1:p.Cys369Tyr missense NM_001406779.1:c.935_936delGCinsAT NP_001393708.1:p.Cys312Tyr missense NM_001406780.1:c.935_936delGCinsAT NP_001393709.1:p.Cys312Tyr missense NM_001406781.1:c.935_936delGCinsAT NP_001393710.1:p.Cys312Tyr missense NM_001406782.1:c.935_936delGCinsAT NP_001393711.1:p.Cys312Tyr missense NM_001406783.1:c.806_807delGCinsAT NP_001393712.1:p.Cys269Tyr missense NM_001406784.1:c.842_843delGCinsAT NP_001393713.1:p.Cys281Tyr missense NM_001406786.1:c.806_807delGCinsAT NP_001393715.1:p.Cys269Tyr missense NM_001406787.1:c.935_936delGCinsAT NP_001393716.1:p.Cys312Tyr missense NM_001406788.1:c.647_648delGCinsAT NP_001393717.1:p.Cys216Tyr missense NM_001406789.1:c.647_648delGCinsAT NP_001393718.1:p.Cys216Tyr missense NM_001406790.1:c.647_648delGCinsAT NP_001393719.1:p.Cys216Tyr missense NM_001406792.1:c.383_384delGCinsAT NP_001393721.1:p.Cys128Tyr missense NM_001406793.1:c.383_384delGCinsAT NP_001393722.1:p.Cys128Tyr missense NM_001406794.1:c.383_384delGCinsAT NP_001393723.1:p.Cys128Tyr missense NM_020629.2:c.1832_1833delGCinsAT NP_065680.1:p.Cys611Tyr missense NM_020630.7:c.1832_1833delGCinsAT NP_065681.1:p.Cys611Tyr missense NC_000010.11:g.43113628_43113629delinsAT NC_000010.10:g.43609076_43609077delinsAT NG_007489.1:g.41560_41561delinsAT LRG_518:g.41560_41561delinsAT LRG_518t1:c.1832_1833delGCinsAT LRG_518p1:p.Cys611Tyr LRG_518t2:c.1832_1833delGCinsAT LRG_518p2:p.Cys611Tyr - Protein change
- C611Y, C357Y, C216Y, C281Y, C515Y, C128Y, C269Y, C479Y, C568Y, C312Y, C369Y, C436Y, C465Y
- Other names
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- Canonical SPDI
- NC_000010.11:43113627:GC:AT
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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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- 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 |
3381 | 3502 |
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
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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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Pathogenic (1) |
criteria provided, single submitter
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Apr 12, 2022 | RCV003062257.2 |
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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Pathogenic
(Apr 12, 2022)
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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: SCV003441426.2
First in ClinVar: Feb 07, 2023 Last updated: Feb 14, 2024 |
Comment:
This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 611 of the RET protein … (more)
This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 611 of the RET protein (p.Cys611Tyr). Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. This missense change has been observed in individual(s) with pheochromocytoma or multiple endocrine neoplasia type 2 (PMID: 8557249, 11395220, 25720320, 28099363). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Not Available"). Experimental studies have shown that this missense change affects RET function (PMID: 9230192). For these reasons, this variant has been classified as Pathogenic. (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
HelpTitle | Author | Journal | Year | Link |
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SDHB/SDHA immunohistochemistry in pheochromocytomas and paragangliomas: a multicenter interobserver variation analysis using virtual microscopy: a Multinational Study of the European Network for the Study of Adrenal Tumors (ENS@T). | Papathomas TG | Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc | 2015 | PMID: 25720320 |
Unusual clinical presentation of a patient with multiple endocrine neoplasia type 2A. | Schuurman B | The Netherlands journal of medicine | 2001 | PMID: 11395220 |
Biological properties of Ret with cysteine mutations correlate with multiple endocrine neoplasia type 2A, familial medullary thyroid carcinoma, and Hirschsprung's disease phenotype. | Ito S | Cancer research | 1997 | PMID: 9230192 |
Mutation analysis of the RET proto-oncogene in Dutch families with MEN 2A, MEN 2B and FMTC: two novel mutations and one de novo mutation for MEN 2A. | Landsvater RM | Human genetics | 1996 | PMID: 8557249 |
Text-mined citations for rs377767398 ...
HelpRecord last updated Feb 14, 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.