Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000574516 | SCV000670069 | uncertain significance | Hereditary cancer-predisposing syndrome | 2017-04-25 | criteria provided, single submitter | clinical testing | Lines of evidence used in support of classification: Insufficient evidence |
| Invitae | RCV000801218 | SCV000940985 | uncertain significance | Hereditary nonpolyposis colon cancer | 2018-10-03 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine with arginine at codon 1330 of the MSH6 protein (p.Leu1330Arg). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and arginine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with MSH6-related disease. ClinVar contains an entry for this variant (Variation ID: 483854). 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. |