NM_000245.4(MET):c.321A>T (p.Leu107Phe) AND Renal cell carcinoma

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 24, 2022
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:: RCV001321872.8

Allele description [Variation Report for NM_000245.4(MET):c.321A>T (p.Leu107Phe)]

NM_000245.4(MET):c.321A>T (p.Leu107Phe)

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.321A>T (p.Leu107Phe)

HGVS:

NC_000007.14:g.116699405A>T
NG_008996.1:g.32001A>T
NM_000245.4:c.321A>TMANE SELECT
NM_001127500.1:c.321A>T
NM_001127500.3:c.321A>T
NM_001324401.3:c.321A>T
NM_001324402.2:c.-91+26828A>T
NP_000236.2:p.Leu107Phe
NP_001120972.1:p.Leu107Phe
NP_001311330.1:p.Leu107Phe
LRG_662t1:c.321A>T
LRG_662:g.32001A>T
NC_000007.13:g.116339459A>T

Protein change:

L107F

Links:

dbSNP: rs1040920548

NCBI 1000 Genomes Browser:

rs1040920548

Molecular consequence:

NM_001324402.2:c.-91+26828A>T - intron variant - [Sequence Ontology: SO:0001627]
NM_000245.4:c.321A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001127500.3:c.321A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001324401.3:c.321A>T - 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
SCV001512723	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 24, 2022)	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

SCV001512723

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 24, 2022)

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, SCV001512723.5

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

Description

This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MET-related conditions. ClinVar contains an entry for this variant (Variation ID: 1022015). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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. This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 107 of the MET protein (p.Leu107Phe).

#	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: Feb 16, 2025

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