Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000115441 | SCV000149350 | uncertain significance | not provided | 2023-09-13 | 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; Observed in an individual with a non-colorectal tumor displaying mismatch repair deficiency (Le et al., 2017); This variant is associated with the following publications: (PMID: 21437237, 28596308, 29245953) |
Counsyl | RCV000410116 | SCV000488711 | uncertain significance | Lynch syndrome 5 | 2016-05-26 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000466432 | SCV000551269 | likely benign | Hereditary nonpolyposis colorectal neoplasms | 2023-12-04 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV000566072 | SCV000662437 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-08-23 | criteria provided, single submitter | clinical testing | The p.E228K variant (also known as c.682G>A), located in coding exon 4 of the MSH6 gene, results from a G to A substitution at nucleotide position 682. The glutamic acid at codon 228 is replaced by lysine, an amino acid with similar properties. This amino acid position is 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. |
Color Diagnostics, |
RCV000566072 | SCV000690470 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-03-15 | criteria provided, single submitter | clinical testing | This missense variant replaces glutamic acid with lysine at codon 228 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 been observed in an individual affected with colorectal cancer (PMID: 29245953) and another individual affected with unspecified cancer (PMID: 28596308). This variant has been identified in 1/250430 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. |
Myriad Genetics, |
RCV000410116 | SCV004018989 | 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 | RCV003467044 | SCV004195709 | uncertain significance | Endometrial carcinoma | 2023-06-23 | criteria provided, single submitter | clinical testing | |
All of Us Research Program, |
RCV003997255 | SCV004836808 | uncertain significance | Lynch syndrome | 2023-10-02 | criteria provided, single submitter | clinical testing | This missense variant replaces glutamic acid with lysine at codon 228 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 been observed in an individual affected with colorectal cancer (PMID: 29245953) and another individual affected with unspecified cancer that is non-colorectal (PMID: 28596308). This variant has been identified in 1/250430 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. |