Total submissions: 11
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000766290 | SCV000211332 | uncertain significance | not provided | 2022-03-29 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 17531815, 21120944, 12019211) |
Invitae | RCV000229406 | SCV000283840 | likely benign | Hereditary nonpolyposis colorectal neoplasms | 2023-08-31 | criteria provided, single submitter | clinical testing | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000766290 | SCV000601601 | uncertain significance | not provided | 2021-08-26 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV000576090 | SCV000670006 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-07-20 | criteria provided, single submitter | clinical testing | The p.A1347P variant (also known as c.4039G>C), located in coding exon 10 of the MSH6 gene, results from a G to C substitution at nucleotide position 4039. The alanine at codon 1347 is replaced by proline, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Counsyl | RCV000663168 | SCV000786329 | uncertain significance | Lynch syndrome 5 | 2018-04-09 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV000576090 | SCV000908443 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-05-31 | criteria provided, single submitter | clinical testing | This missense variant replaces alanine with proline at codon 1347 of the MSH6 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with MSH6-related disorders in the literature. This variant has been identified in 1/250856 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
Laboratory for Molecular Medicine, |
RCV000160703 | SCV000966670 | uncertain significance | not specified | 2018-10-17 | criteria provided, single submitter | clinical testing | The p.Ala1347Pro variant in MSH6 has not been reported in the literature in indi viduals with MSH6-associated cancers, but has been reported by other clinical la boratories in ClinVar (Variation ID: 182650). This variant has also been identif ied in 1/111534 European chromosomes by gnomAD (http://gnomad.broadinstitute.org ). Computational prediction tools and conservation analysis suggest that the p.A la1347Pro variant may not impact the protein, though this information is not pre dictive enough to rule out pathogenicity. In summary, the clinical significance of the p.Ala1347Pro variant is uncertain. ACMG/AMP Criteria applied: BP4, PM2. |
CHEO Genetics Diagnostic Laboratory, |
RCV001798555 | SCV002042058 | uncertain significance | Breast and/or ovarian cancer | 2020-11-06 | criteria provided, single submitter | clinical testing | |
Myriad Genetics, |
RCV000663168 | SCV004019025 | uncertain significance | Lynch syndrome 5 | 2023-03-29 | criteria provided, single submitter | clinical testing | This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk. |
Baylor Genetics | RCV003462097 | SCV004197622 | uncertain significance | Endometrial carcinoma | 2023-10-16 | criteria provided, single submitter | clinical testing | |
All of Us Research Program, |
RCV003998506 | SCV004835199 | uncertain significance | Lynch syndrome | 2023-10-30 | criteria provided, single submitter | clinical testing | This missense variant replaces alanine with proline at codon 1347 of the MSH6 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with MSH6-related disorders in the literature. This variant has been identified in 1/250856 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |