NM_000245.4(MET):c.2864T>A (p.Leu955Gln) AND Renal cell carcinoma

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 27, 2016
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:: RCV001306836.5

Allele description [Variation Report for NM_000245.4(MET):c.2864T>A (p.Leu955Gln)]

NM_000245.4(MET):c.2864T>A (p.Leu955Gln)

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.2864T>A (p.Leu955Gln)

HGVS:

NC_000007.14:g.116771631T>A
NG_008996.1:g.104227T>A
NM_000245.4:c.2864T>AMANE SELECT
NM_001127500.3:c.2918T>A
NM_001324402.2:c.1574T>A
NP_000236.2:p.Leu955Gln
NP_001120972.1:p.Leu973Gln
NP_001311331.1:p.Leu525Gln
LRG_662t1:c.2918T>A
LRG_662:g.104227T>A
NC_000007.13:g.116411685T>A
NM_001127500.1:c.2918T>A

Protein change:

L525Q

Links:

dbSNP: rs879254335

NCBI 1000 Genomes Browser:

rs879254335

Molecular consequence:

NM_000245.4:c.2864T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001127500.3:c.2918T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001324402.2:c.1574T>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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Mus musculus cDNA clone IMAGE:40109548
Mus musculus cDNA clone IMAGE:40109548
gi|156229789|gb|BC152364.1|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001496220	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 27, 2016)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001496220

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 27, 2016)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

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, SCV001496220.4

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

Description

In summary, this variant is a novel missense change with uncertain impact on protein function and splicing. It has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on mRNA splicing suggest that this variant may alter mRNA splicing, but this prediction has not been confirmed by published transcriptional studies. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a MET-related disease. This sequence change replaces leucine with glutamine at codon 973 of the MET protein (p.Leu973Gln). The leucine residue is weakly conserved and there is a moderate physicochemical difference between leucine and glutamine.

#	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: Nov 10, 2024

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