Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000825371 | SCV000966666 | uncertain significance | not specified | 2018-10-16 | criteria provided, single submitter | clinical testing | The p.Ala350Pro variant in MSH6 has not been reported in individuals with MSH6-a ssociated cancers or in large population databases. Computational prediction too ls and conservation analysis suggest that the p.Ala350Pro variant may not impact the protein. In summary, the clinical significance of the p.Ala350Pro variant i s uncertain. ACMG/AMP Criteria applied: BP4, PM2. |
Invitae | RCV001211394 | SCV001382932 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2019-10-09 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with MSH6-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with proline at codon 350 of the MSH6 protein (p.Ala350Pro). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and proline. |