Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
International Society for Gastrointestinal Hereditary Tumours |
RCV000680207 | SCV000807671 | likely benign | Lynch syndrome 1 | 2018-06-13 | reviewed by expert panel | curation | Multifactorial likelihood analysis posterior probability < 0.05 (0.028) |
Invitae | RCV000560586 | SCV000624656 | likely benign | Hereditary nonpolyposis colorectal neoplasms | 2023-09-13 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV000567174 | SCV000662526 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-07-11 | criteria provided, single submitter | clinical testing | The p.C496Y variant (also known as c.1487G>A), located in coding exon 4 of the MSH6 gene, results from a G to A substitution at nucleotide position 1487. The cysteine at codon 496 is replaced by tyrosine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Color Diagnostics, |
RCV000567174 | SCV002052944 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-12-08 | criteria provided, single submitter | clinical testing | This missense variant replaces cysteine with tyrosine at codon 496 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). A functional study reported that in vitro mismatch repair activity of this variant was 45.8% of wild type protein (PMID: 31965077). This variant has not been reported in individuals affected with MSH6-related disorders in the literature. This variant has been identified in 3/251230 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. |
Sema4, |
RCV000567174 | SCV002535628 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-10-11 | criteria provided, single submitter | curation | |
All of Us Research Program, |
RCV004003662 | SCV004843710 | uncertain significance | Lynch syndrome | 2023-02-24 | criteria provided, single submitter | clinical testing | This missense variant replaces cysteine with tyrosine at codon 496 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). A functional study reported that in vitro mismatch repair activity of this variant was 45.8% of wild type protein (PMID: 31965077). This variant has not been reported in individuals affected with MSH6-related disorders in the literature. This variant has been identified in 3/251230 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. |