Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000571714 | SCV000676152 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-10-08 | criteria provided, single submitter | clinical testing | The p.A168V variant (also known as c.503C>T), located in coding exon 3 of the MSH6 gene, results from a C to T substitution at nucleotide position 503. The alanine at codon 168 is replaced by valine, an amino acid with similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
St. |
RCV001526810 | SCV001737454 | uncertain significance | Lynch syndrome 5 | 2021-03-31 | criteria provided, single submitter | clinical testing | The MSH6 c.503C>T (p.Ala168Val) missense change is absent in gnomAD v2.1.1 (PM2_Supporting; https://gnomad.broadinstitute.org/). Six of seven in silico tools predict a benign effect of this variant on protein function (BP4), but to our knowledge these predictions have not been confirmed by functional assays. To our knowledge, this variant has not been reported in individuals with Lynch syndrome or CMMRD. In summary, this variant meets criteria to be classified as of uncertain significance based on the ACMG/AMP criteria: PM2_Supporting, BP4. |