Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000219210 | SCV000276061 | likely benign | Hereditary cancer-predisposing syndrome | 2019-03-19 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| Gene |
RCV001705217 | SCV000517972 | likely benign | not provided | 2020-03-06 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000697068 | SCV000825658 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2022-09-30 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with serine, which is neutral and polar, at codon 62 of the MSH6 protein (p.Arg62Ser). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with MSH6-related conditions. ClinVar contains an entry for this variant (Variation ID: 232033). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt MSH6 protein function. 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. |
| Color Diagnostics, |
RCV000219210 | SCV000903697 | likely benign | Hereditary cancer-predisposing syndrome | 2018-09-07 | criteria provided, single submitter | clinical testing | |
| Sema4, |
RCV000219210 | SCV002535667 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-10-11 | criteria provided, single submitter | curation | |
| All of Us Research Program, |
RCV003997941 | SCV004830459 | likely benign | Lynch syndrome | 2023-12-18 | criteria provided, single submitter | clinical testing |