Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000166149 | SCV000216921 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-02-01 | criteria provided, single submitter | clinical testing | The p.R901C variant (also known as c.2701C>T), located in coding exon 4 of the MSH6 gene, results from a C to T substitution at nucleotide position 2701. The arginine at codon 901 is replaced by cysteine, an amino acid with highly dissimilar 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. |
Invitae | RCV000456613 | SCV000551182 | likely benign | Hereditary nonpolyposis colorectal neoplasms | 2023-12-07 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV000166149 | SCV001340277 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-02-02 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with cysteine at codon 901 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 1/250654 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. |
Gene |
RCV001775649 | SCV002013549 | uncertain significance | not provided | 2023-08-31 | 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) |
Baylor Genetics | RCV003462201 | SCV004197630 | uncertain significance | Endometrial carcinoma | 2023-10-13 | criteria provided, single submitter | clinical testing | |
All of Us Research Program, |
RCV003995483 | SCV004840717 | uncertain significance | Lynch syndrome | 2023-03-07 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with cysteine at codon 901 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). 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 1/250654 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. |