Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000130614 | SCV000185490 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-02-12 | criteria provided, single submitter | clinical testing | The p.Q132E variant (also known as c.394C>G), located in coding exon 2 of the MSH6 gene, results from a C to G substitution at nucleotide position 394. The glutamine at codon 132 is replaced by glutamic acid, an amino acid with highly similar properties. This amino acid position is well 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. |
Labcorp Genetics |
RCV000691637 | SCV000819423 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2021-09-01 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine with glutamic acid at codon 132 of the MSH6 protein (p.Gln132Glu). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and glutamic acid. This variant is not present in population databases (ExAC no frequency). 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: 141907). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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, |
RCV000130614 | SCV001352505 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-03-14 | criteria provided, single submitter | clinical testing |