ClinVar Genomic variation as it relates to human health
NM_020975.6(RET):c.1780C>T (p.His594Tyr)
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.1780C>T (p.His594Tyr)
Variation ID: 937751 Accession: VCV000937751.8
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 10q11.21 10: 43113576 (GRCh38) [ NCBI UCSC ] 10: 43609024 (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 Jul 16, 2020 Feb 20, 2024 Oct 13, 2022 - HGVS
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Nucleotide Protein Molecular
consequenceNM_020975.6:c.1780C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_066124.1:p.His594Tyr missense NM_000323.2:c.1780C>T NP_000314.1:p.His594Tyr missense NM_001355216.2:c.1018C>T NP_001342145.1:p.His340Tyr missense NM_001406743.1:c.1780C>T NP_001393672.1:p.His594Tyr missense NM_001406744.1:c.1780C>T NP_001393673.1:p.His594Tyr missense NM_001406759.1:c.1780C>T NP_001393688.1:p.His594Tyr missense NM_001406760.1:c.1780C>T NP_001393689.1:p.His594Tyr missense NM_001406761.1:c.1651C>T NP_001393690.1:p.His551Tyr missense NM_001406762.1:c.1651C>T NP_001393691.1:p.His551Tyr missense NM_001406763.1:c.1780C>T NP_001393692.1:p.His594Tyr missense NM_001406764.1:c.1651C>T NP_001393693.1:p.His551Tyr missense NM_001406765.1:c.1780C>T NP_001393694.1:p.His594Tyr missense NM_001406766.1:c.1492C>T NP_001393695.1:p.His498Tyr missense NM_001406767.1:c.1492C>T NP_001393696.1:p.His498Tyr missense NM_001406768.1:c.1651C>T NP_001393697.1:p.His551Tyr missense NM_001406769.1:c.1384C>T NP_001393698.1:p.His462Tyr missense NM_001406770.1:c.1492C>T NP_001393699.1:p.His498Tyr missense NM_001406771.1:c.1342C>T NP_001393700.1:p.His448Tyr missense NM_001406772.1:c.1384C>T NP_001393701.1:p.His462Tyr missense NM_001406773.1:c.1342C>T NP_001393702.1:p.His448Tyr missense NM_001406774.1:c.1255C>T NP_001393703.1:p.His419Tyr missense NM_001406775.1:c.1054C>T NP_001393704.1:p.His352Tyr missense NM_001406776.1:c.1054C>T NP_001393705.1:p.His352Tyr missense NM_001406777.1:c.1054C>T NP_001393706.1:p.His352Tyr missense NM_001406778.1:c.1054C>T NP_001393707.1:p.His352Tyr missense NM_001406779.1:c.883C>T NP_001393708.1:p.His295Tyr missense NM_001406780.1:c.883C>T NP_001393709.1:p.His295Tyr missense NM_001406781.1:c.883C>T NP_001393710.1:p.His295Tyr missense NM_001406782.1:c.883C>T NP_001393711.1:p.His295Tyr missense NM_001406783.1:c.754C>T NP_001393712.1:p.His252Tyr missense NM_001406784.1:c.790C>T NP_001393713.1:p.His264Tyr missense NM_001406786.1:c.754C>T NP_001393715.1:p.His252Tyr missense NM_001406787.1:c.883C>T NP_001393716.1:p.His295Tyr missense NM_001406788.1:c.595C>T NP_001393717.1:p.His199Tyr missense NM_001406789.1:c.595C>T NP_001393718.1:p.His199Tyr missense NM_001406790.1:c.595C>T NP_001393719.1:p.His199Tyr missense NM_001406792.1:c.331C>T NP_001393721.1:p.His111Tyr missense NM_001406793.1:c.331C>T NP_001393722.1:p.His111Tyr missense NM_001406794.1:c.331C>T NP_001393723.1:p.His111Tyr missense NM_020629.2:c.1780C>T NP_065680.1:p.His594Tyr missense NM_020630.7:c.1780C>T NP_065681.1:p.His594Tyr missense NC_000010.11:g.43113576C>T NC_000010.10:g.43609024C>T NG_007489.1:g.41508C>T LRG_518:g.41508C>T LRG_518t1:c.1780C>T LRG_518p1:p.His594Tyr LRG_518t2:c.1780C>T LRG_518p2:p.His594Tyr - Protein change
- H340Y, H594Y, H252Y, H419Y, H462Y, H498Y, H111Y, H264Y, H352Y, H448Y, H551Y, H199Y, H295Y
- Other names
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- Canonical SPDI
- NC_000010.11:43113575: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.
The Genome Aggregation Database (gnomAD), exomes 0.00000
Exome Aggregation Consortium (ExAC) 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 |
3592 | 3714 |
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
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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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Oct 13, 2022 | RCV001206841.8 |
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
(Oct 13, 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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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001378170.5
First in ClinVar: Jul 16, 2020 Last updated: Feb 20, 2024 |
Comment:
The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD … (more)
The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The tyrosine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 937751). This variant has not been reported in the literature in individuals affected with RET-related conditions. This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 594 of the RET protein (p.His594Tyr). (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 rs778622905 ...
HelpRecord last updated Sep 29, 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.