NM_000245.4(MET):c.2209A>G (p.Ser737Gly) AND not specified

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:: RCV001844258.1

Allele description [Variation Report for NM_000245.4(MET):c.2209A>G (p.Ser737Gly)]

NM_000245.4(MET):c.2209A>G (p.Ser737Gly)

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.2209A>G (p.Ser737Gly)

HGVS:

NC_000007.14:g.116758565A>G
NG_008996.1:g.91161A>G
NM_000245.4:c.2209A>GMANE SELECT
NM_001127500.3:c.2209A>G
NM_001324401.3:c.2209A>G
NM_001324402.2:c.919A>G
NP_000236.2:p.Ser737Gly
NP_001120972.1:p.Ser737Gly
NP_001311330.1:p.Ser737Gly
NP_001311331.1:p.Ser307Gly
LRG_662t1:c.2209A>G
LRG_662:g.91161A>G
NC_000007.13:g.116398619A>G
NM_001127500.1:c.2209A>G
NM_001127500.2:c.2209A>G

Protein change:

S307G

Links:

dbSNP: rs755571526

NCBI 1000 Genomes Browser:

rs755571526

Molecular consequence:

NM_000245.4:c.2209A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001127500.3:c.2209A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001324401.3:c.2209A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001324402.2:c.919A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002103587	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Feb 24, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002103587

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Feb 24, 2022)

germline

clinical testing

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

Citation Link

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

Genomic profiling of Chinese patients with urothelial carcinoma.

Yang B, Zhao X, Wan C, Ma X, Niu S, Guo A, Wang J, Wang J, Sun D, Jiao S.

BMC Cancer. 2021 Feb 15;21(1):162. doi: 10.1186/s12885-021-07829-1.

PubMed [citation]

PMID:: 33588785
PMCID:: PMC7885246

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV002103587.1

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

Description

Variant summary: MET c.2209A>G (p.Ser737Gly) results in a non-conservative amino acid change located in the 2nd IPT (Ig-like, plexins, transcription factors) domain (IPR002909) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 249220 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. The variant, c.2209A>G, has been reported in the literature as a germline variant in an individual affected with bladder carcinoma. This report however does not provide unequivocal conclusions about association of the variant with Papillary Renal Cell Carcinoma. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

#	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 25, 2025

ClinVar

Relating variation to medicine