Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000484550 | SCV000567916 | uncertain significance | not provided | 2015-09-09 | criteria provided, single submitter | clinical testing | This variant is denoted MSH6 c.787G>C at the cDNA level, p.Val263Leu (V263L) at the protein level, and results in the change of a Valine to a Leucine (GTG>CTG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. MSH6 Val263Leu was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Since Valine and Leucine share similar properties, this is considered a conservative amino acid substitution. MSH6 Val263Leu occurs at a position that is conserved in mammals and is not located in a known functional domain (Kariola 2002, Terui 2013, UniProt). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available information, it is unclear whether MSH6 Val263Leu is pathogenic or benign. We consider it to be a variant of uncertain significance. |
| Labcorp Genetics |
RCV001308254 | SCV001497694 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2022-08-09 | 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. 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. ClinVar contains an entry for this variant (Variation ID: 419819). This variant has not been reported in the literature in individuals affected with MSH6-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 263 of the MSH6 protein (p.Val263Leu). |
| Baylor Genetics | RCV004568169 | SCV005054865 | uncertain significance | Endometrial carcinoma | 2024-03-08 | criteria provided, single submitter | clinical testing |