Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001048678 | SCV001212693 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2022-12-17 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with MSH2-related conditions. 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. Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 33357406) indicates that this missense variant is expected to disrupt MSH2 function. ClinVar contains an entry for this variant (Variation ID: 845581). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces phenylalanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 836 of the MSH2 protein (p.Phe836Ser). |
Color Diagnostics, |
RCV001179052 | SCV001343632 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-01-03 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV001179052 | SCV002745114 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-08-22 | criteria provided, single submitter | clinical testing | The p.F836S variant (also known as c.2507T>C), located in coding exon 15 of the MSH2 gene, results from a T to C substitution at nucleotide position 2507. The phenylalanine at codon 836 is replaced by serine, an amino acid with highly dissimilar properties. 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. |