ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.448G>T (p.Val150Phe)

dbSNP: rs1558459157
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Cancer Genomics Group, Japanese Foundation For Cancer Research RCV001030706 SCV001193628 uncertain significance Hereditary breast ovarian cancer syndrome 2019-05-01 criteria provided, single submitter research
Mendelics RCV002249638 SCV002518256 uncertain significance not specified 2022-05-04 criteria provided, single submitter clinical testing
Ambry Genetics RCV002327243 SCV002639668 likely benign Hereditary cancer-predisposing syndrome 2022-08-02 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.
Department of Pathology and Laboratory Medicine, Sinai Health System RCV001357699 SCV001553245 uncertain significance Lynch syndrome no assertion criteria provided clinical testing The MSH2 p.Val150Phe variant was not identified in the literature nor was it identified in the dbSNP, ClinVar, or UMD-LSDB databases. The variant was not identified in the following control databases: the Exome Aggregation Consortium (August 8th 2016) or the Genome Aggregation Database (Feb 27, 2017). The p.Val150 residue is not conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) 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 (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in 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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