Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000166850 | SCV000217665 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-03-08 | criteria provided, single submitter | clinical testing | The p.H1207D variant (also known as c.3619C>G), located in coding exon 7 of the MSH6 gene, results from a C to G substitution at nucleotide position 3619. The histidine at codon 1207 is replaced by aspartic acid, an amino acid with similar properties. This variant was reported in 1/60,466 breast cancer cases and in 0/53,461 controls (Dorling et al. N Engl J Med. 2021 02;384:428-439). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this alteration remains unclear. |
| Gene |
RCV000484988 | SCV000566273 | uncertain significance | not provided | 2022-10-28 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on 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) |
| Labcorp Genetics |
RCV000629789 | SCV000750745 | likely benign | Hereditary nonpolyposis colorectal neoplasms | 2024-04-22 | criteria provided, single submitter | clinical testing | |
| Color Diagnostics, |
RCV000166850 | SCV000908424 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-03-15 | criteria provided, single submitter | clinical testing | This missense variant replaces histidine with aspartic acid at codon 1207 of the MSH6 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. In a large breast cancer case-control study, this variant has been reported in 1/60466 cases and 0/53461 unaffected controls (PMID: 33471991). This variant has been identified in 1/251440 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. |