Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001021223 | SCV001182809 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-11-20 | criteria provided, single submitter | clinical testing | The p.N1273S variant (also known as c.3818A>G), located in coding exon 9 of the MSH6 gene, results from an A to G substitution at nucleotide position 3818. The asparagine at codon 1273 is replaced by serine, an amino acid with highly similar properties. This amino acid position is highly 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. |
Color Diagnostics, |
RCV001021223 | SCV001344757 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-05-10 | criteria provided, single submitter | clinical testing | This missense variant replaces asparagine with serine at codon 1273 of the MSH6 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/245910 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. |
Invitae | RCV001861012 | SCV002150538 | likely benign | Hereditary nonpolyposis colorectal neoplasms | 2023-05-15 | criteria provided, single submitter | clinical testing | |
All of Us Research Program, |
RCV004004611 | SCV004835146 | uncertain significance | Lynch syndrome | 2023-05-31 | criteria provided, single submitter | clinical testing | This missense variant replaces asparagine with serine at codon 1273 of the MSH6 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/245910 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. |