Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002339837 | SCV002619325 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2024-03-27 | criteria provided, single submitter | clinical testing | The p.A1198P variant (also known as c.3592G>C), located in coding exon 7 of the MSH6 gene, results from a G to C substitution at nucleotide position 3592. The alanine at codon 1198 is replaced by proline, an amino acid with highly similar properties. This variant has been identified in a proband whose Lynch syndrome-associated tumor demonstrated high microsatellite instability and isolated loss of MSH6 expression by immunohistochemistry (Ambry internal data). Based on internal structural analysis, this residue is on the interface with MSH2 and p.A1198P is very destabilizing to the local structure (Ambry internal data). This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
Fulgent Genetics, |
RCV005025796 | SCV005658592 | likely pathogenic | Endometrial carcinoma; Lynch syndrome 5; Mismatch repair cancer syndrome 3 | 2024-05-02 | criteria provided, single submitter | clinical testing |