ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.64T>A (p.Phe22Ile)

dbSNP: rs1189127007
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mendelics RCV000708824 SCV000837811 uncertain significance Lynch syndrome 2018-07-02 criteria provided, single submitter clinical testing
Invitae RCV001052926 SCV001217162 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2023-10-20 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 22 of the MSH2 protein (p.Phe22Ile). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Lynch syndrome (PMID: 31391288). ClinVar contains an entry for this variant (Variation ID: 584604). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 33357406) indicates that this missense variant is not expected to disrupt MSH2 function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV002360839 SCV002659265 uncertain significance Hereditary cancer-predisposing syndrome 2020-03-29 criteria provided, single submitter clinical testing The p.F22I variant (also known as c.64T>A), located in coding exon 1 of the MSH2 gene, results from a T to A substitution at nucleotide position 64. The phenylalanine at codon 22 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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