ClinVar Miner

Submissions for variant NM_000245.4(MET):c.901A>G (p.Thr301Ala)

gnomAD frequency: 0.00038  dbSNP: rs201687037
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000153491 SCV000203009 uncertain significance not provided 2014-01-15 criteria provided, single submitter clinical testing
Ambry Genetics RCV000164028 SCV000214633 likely benign Hereditary cancer-predisposing syndrome 2018-09-10 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Labcorp Genetics (formerly Invitae), Labcorp RCV000198491 SCV000254696 likely benign Renal cell carcinoma 2024-01-29 criteria provided, single submitter clinical testing
Baylor Genetics RCV001333796 SCV001526480 uncertain significance Autosomal recessive nonsyndromic hearing loss 97 2018-05-14 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
GeneDx RCV000153491 SCV001772189 uncertain significance not provided 2024-03-26 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 37316882, 27696107, 34882875)
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000153491 SCV002049877 uncertain significance not provided 2023-10-23 criteria provided, single submitter clinical testing The MET c.901A>G, p.Thr301Ala variant (rs201687037), to our knowledge, has not been reported in the medical literature; however, this variant is listed in the ClinVar database (Variation ID: 167292). This variant is found in the general population with an overall allele frequency of 0.03% (81/280,300 alleles) in the Genome Aggregation Database. The threonine at codon 301 is moderately conserved, and computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.243). Based on the available information, the clinical significance of this variant is uncertain.
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV002267890 SCV002550774 uncertain significance not specified 2024-07-31 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000153491 SCV005622941 uncertain significance not provided 2023-11-13 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System RCV000153491 SCV001553583 uncertain significance not provided no assertion criteria provided clinical testing The MET p.T301A variant was identified in one individual with colon cancer (Rohlin_2017_PMID: 27696107). The variant was identified in dbSNP (ID: rs201687037), ClinVar (classified as uncertain significance by EGL Genetic Diagnostics and Invitae; and as likely benign by Ambry Genetics), and COSMIC (lung, prostate, endometrium). The variant was identified in control databases in 81 of 280300 chromosomes at a frequency of 0.0002890, and was observed at the highest frequency in the European (non-Finnish) population in 71 of 128168 chromosomes (freq: 0.0005540) (Genome Aggregation Database March 6, 2019, v2.1.1). The p.T301 residue is conserved in mammals and computational analyses (MUT Assesor, PolyPhen-2, SIFT, MutationTaster, Revel, FATHMM, MetaLR, DANN) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (Splice AI exome) do not predict an impact on splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.

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