NM_000245.4(MET):c.2362G>A (p.Val788Met) AND Renal cell carcinoma

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 26, 2021
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV000690097.9

Allele description [Variation Report for NM_000245.4(MET):c.2362G>A (p.Val788Met)]

NM_000245.4(MET):c.2362G>A (p.Val788Met)

Gene:

MET:MET proto-oncogene, receptor tyrosine kinase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7q31.2

Genomic location:

Preferred name:

NM_000245.4(MET):c.2362G>A (p.Val788Met)

HGVS:

NC_000007.14:g.116759488G>A
NG_008996.1:g.92084G>A
NM_000245.4:c.2362G>AMANE SELECT
NM_001127500.3:c.2416G>A
NM_001324401.3:c.2362G>A
NM_001324402.2:c.1072G>A
NP_000236.2:p.Val788Met
NP_001120972.1:p.Val806Met
NP_001311330.1:p.Val788Met
NP_001311331.1:p.Val358Met
LRG_662t1:c.2416G>A
LRG_662:g.92084G>A
NC_000007.13:g.116399542G>A
NM_001127500.1:c.2416G>A

Protein change:

V358M

Links:

dbSNP: rs1489302008

NCBI 1000 Genomes Browser:

rs1489302008

Molecular consequence:

NM_000245.4:c.2362G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001127500.3:c.2416G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001324401.3:c.2362G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001324402.2:c.1072G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Renal cell carcinoma (RCCP1)
Identifiers:: MONDO: MONDO:0005086; MeSH: D002292; MedGen: C0007134; Human Phenotype Ontology: HP:0005584

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000817774	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 26, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 26700204, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000817774

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 26, 2021)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Recurrent Mutations of Chromatin-Remodeling Genes and Kinase Receptors in Pheochromocytomas and Paragangliomas.

Toledo RA, Qin Y, Cheng ZM, Gao Q, Iwata S, Silva GM, Prasad ML, Ocal IT, Rao S, Aronin N, Barontini M, Bruder J, Reddick RL, Chen Y, Aguiar RC, Dahia PL.

Clin Cancer Res. 2016 May 1;22(9):2301-10. doi: 10.1158/1078-0432.CCR-15-1841. Epub 2015 Dec 23.

PubMed [citation]

PMID:: 26700204
PMCID:: PMC4854762

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000817774.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This variant is not present in population databases (ExAC no frequency). This sequence change replaces valine with methionine at codon 806 of the MET protein (p.Val806Met). The valine residue is highly conserved and there is a small physicochemical difference between valine and methionine. This variant has been observed in a family affected with pheochromocytoma (PMID: 26700204). ClinVar contains an entry for this variant (Variation ID: 569466). 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0").

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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