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NM_000245.4(MET):c.2971C>T (p.Pro991Ser) AND Hereditary cancer-predisposing syndrome

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Apr 14, 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:
RCV001018130.3

Allele description [Variation Report for NM_000245.4(MET):c.2971C>T (p.Pro991Ser)]

NM_000245.4(MET):c.2971C>T (p.Pro991Ser)

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.2971C>T (p.Pro991Ser)
HGVS:
  • NC_000007.14:g.116771932C>T
  • NG_008996.1:g.104528C>T
  • NM_000245.4:c.2971C>TMANE SELECT
  • NM_001127500.3:c.3025C>T
  • NM_001324402.2:c.1681C>T
  • NP_000236.2:p.Pro991Ser
  • NP_001120972.1:p.Pro1009Ser
  • NP_001311331.1:p.Pro561Ser
  • LRG_662t1:c.3025C>T
  • LRG_662:g.104528C>T
  • NC_000007.13:g.116411986C>T
  • NM_001127500.1:c.3025C>T
  • NM_001127500.2:c.3025C>T
Protein change:
P1009S
Links:
dbSNP: rs768678989
NCBI 1000 Genomes Browser:
rs768678989
Molecular consequence:
  • NM_000245.4:c.2971C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127500.3:c.3025C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001324402.2:c.1681C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Hereditary cancer-predisposing syndrome
Synonyms:
Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001179321Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)
Uncertain significance
(Apr 14, 2022)
germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

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

Citations

PubMed

A novel germ line juxtamembrane Met mutation in human gastric cancer.

Lee JH, Han SU, Cho H, Jennings B, Gerrard B, Dean M, Schmidt L, Zbar B, Vande Woude GF.

Oncogene. 2000 Oct 12;19(43):4947-53.

PubMed [citation]
PMID:
11042681

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
See all PubMed Citations (4)

Details of each submission

From Ambry Genetics, SCV001179321.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

The p.P1009S variant (also known as c.3025C>T), located in coding exon 13 of the MET gene, results from a C to T substitution at nucleotide position 3025. The proline at codon 1009 is replaced by serine, an amino acid with similar properties. This alteration has been reported in a patient with primary gastric cancer (Lee JH et al. Oncogene, 2000 Oct;19:4947-53). Lee et al. (2000) also examined the impact of this alteration in when expressed in a mouse embryonic fibroblast cell line and found it results in increased tyrosine phosphorylation compared to wild-type, as well as highly tumorigenic colony formation in soft agar, leading authors to conclude that it could contribute to tumorigenesis of gastric cancer. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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

Last Updated: Sep 29, 2024