Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002443791 | SCV002736579 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-12-22 | criteria provided, single submitter | clinical testing | The p.S755F variant (also known as c.2264C>T), located in coding exon 14 of the MSH2 gene, results from a C to T substitution at nucleotide position 2264. The serine at codon 755 is replaced by phenylalanine, an amino acid with highly dissimilar properties. In a massively parallel cell-based functional assay testing susceptibility to a DNA damaging agent, 6-thioguanine (6-TG), this variant was reported to be functionally neutral (Jia X et al. Am J Hum Genet, 2021 01;108:163-175). This amino acid position is highly 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. |