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NM_000245.4(MET):c.2318C>T (p.Pro773Leu) AND not provided

Germline classification:
Uncertain significance (6 submissions)
Last evaluated:
Aug 31, 2024
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
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:
RCV001566122.14

Allele description [Variation Report for NM_000245.4(MET):c.2318C>T (p.Pro773Leu)]

NM_000245.4(MET):c.2318C>T (p.Pro773Leu)

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.2318C>T (p.Pro773Leu)
HGVS:
  • NC_000007.14:g.116759444C>T
  • NG_008996.1:g.92040C>T
  • NM_000245.4:c.2318C>TMANE SELECT
  • NM_001127500.3:c.2372C>T
  • NM_001324401.3:c.2318C>T
  • NM_001324402.2:c.1028C>T
  • NP_000236.2:p.Pro773Leu
  • NP_001120972.1:p.Pro791Leu
  • NP_001311330.1:p.Pro773Leu
  • NP_001311331.1:p.Pro343Leu
  • LRG_662t1:c.2372C>T
  • LRG_662:g.92040C>T
  • NC_000007.13:g.116399498C>T
  • NM_001127500.1:c.2372C>T
  • NM_001127500.2:c.2372C>T
Protein change:
P343L
Links:
dbSNP: rs771333219
NCBI 1000 Genomes Browser:
rs771333219
Molecular consequence:
  • NM_000245.4:c.2318C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127500.3:c.2372C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001324401.3:c.2318C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001324402.2:c.1028C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
none provided; RECLASSIFIED - ADRA2C POLYMORPHISM; RECLASSIFIED - ADRB1 POLYMORPHISM
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001789595GeneDx
criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)
Uncertain significance
(Feb 23, 2024)
germlineclinical testing

Citation Link,

SCV001809526Genome Diagnostics Laboratory, Amsterdam University Medical Center - VKGL Data-share Consensus
no assertion criteria provided
Likely benigngermlineclinical testing

SCV001971622Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus

See additional submitters

no assertion criteria provided
Likely benigngermlineclinical testing

SCV002774814Quest Diagnostics Nichols Institute San Juan Capistrano
criteria provided, single submitter

(Quest Diagnostics criteria)
Uncertain significance
(Aug 31, 2024)
unknownclinical testing

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

SCV003800519ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
criteria provided, single submitter

(ARUP Molecular Germline Variant Investigation Process 2021)
Uncertain significance
(Mar 9, 2022)
germlineclinical testing

Citation Link,

SCV003808788Revvity Omics, Revvity
criteria provided, single submitter

(ACMG Guidelines, 2015)
Uncertain significance
(Oct 20, 2023)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

A novel germline mutation in the MET extracellular domain in a Korean patient with the diffuse type of familial gastric cancer.

Kim IJ, Park JH, Kang HC, Shin Y, Lim SB, Ku JL, Yang HK, Lee KU, Park JG.

J Med Genet. 2003 Aug;40(8):e97. No abstract available.

PubMed [citation]
PMID:
12920089
PMCID:
PMC1735541

A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

Karbassi I, Maston GA, Love A, DiVincenzo C, Braastad CD, Elzinga CD, Bright AR, Previte D, Zhang K, Rowland CM, McCarthy M, Lapierre JL, Dubois F, Medeiros KA, Batish SD, Jones J, Liaquat K, Hoffman CA, Jaremko M, Wang Z, Sun W, Buller-Burckle A, et al.

Hum Mutat. 2016 Jan;37(1):127-34. doi: 10.1002/humu.22918. Epub 2015 Oct 29.

PubMed [citation]
PMID:
26467025
PMCID:
PMC4737317
See all PubMed Citations (3)

Details of each submission

From GeneDx, SCV001789595.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

Observed in an individual with familial gastric cancer (PMID: 12920089); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 16000876, 31023376, 12920089, 35977101)

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From Genome Diagnostics Laboratory, Amsterdam University Medical Center - VKGL Data-share Consensus, SCV001809526.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus, SCV001971622.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV002774814.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

The MET c.2372C>T (p.Pro791Leu) variant has been reported in the published literature in a family affected with gastric cancer (PMID: 12920089 (2003)). The frequency of this variant in the general population, 0.00055 (19/34426 chromosomes in Admixed American subpopulation (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is higher than would generally be expected for pathogenic variants in this gene. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV003800519.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The MET c.2372C>T; p.Pro791Leu variant (rs771333219) is reported in the literature in an individual affected with familial gastric cancer (Kim 2003). This variant is reported in ClinVar (Variation ID: 411912) and is found in the Latino population with an allele frequency of 0.06% (19/34426 alleles) in the Genome Aggregation Database. The proline at codon 791 is highly conserved, and computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.303). However, given the lack of clinical and functional data, the significance of the p.Pro791Leu variant is uncertain at this time. References: Kim IJ et al. A novel germline mutation in the MET extracellular domain in a Korean patient with the diffuse type of familial gastric cancer. J Med Genet. 2003 Aug;40(8):e97. PMID: 12920089.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Revvity Omics, Revvity, SCV003808788.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jan 19, 2025