Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000164343 | SCV000214976 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-02-14 | criteria provided, single submitter | clinical testing | The p.P15S variant (also known as c.43C>T), located in coding exon 1 of the MSH6 gene, results from a C to T substitution at nucleotide position 43. The proline at codon 15 is replaced by serine, an amino acid with similar properties. In one study, this alteration was identified in 1/1231 individuals diagnosed with colorectal cancer, who had targeted sequencing of thirty-six known or putative colorectal cancer susceptibility genes (DeRycke MS et al. Mol Genet Genomic Med. 2017 Sep;5:553-569). This alteration has also been identified in multiple individuals diagnosed with breast cancer (Wang J et al. Cancer Med, 2019 May;8:2074-2084; Hu L et al. NPJ Breast Cancer, 2022 Apr;8:52). This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this alteration remains unclear. |
| Color Diagnostics, |
RCV000164343 | SCV000690442 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-08-30 | criteria provided, single submitter | clinical testing | This missense variant replaces proline with serine at codon 15 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 reported in an individual affected with colorectal cancer (PMID: 28944238). This variant has been identified in 6/244720 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. |
| Labcorp Genetics |
RCV000793874 | SCV000933252 | benign | Hereditary nonpolyposis colorectal neoplasms | 2024-01-11 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001795287 | SCV002032545 | uncertain significance | not provided | 2021-11-29 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in an individual with early onset colorectal cancer (DeRycke 2017); This variant is associated with the following publications: (PMID: 22949387, 28944238, 25980754, 22703879) |
| Baylor Genetics | RCV003462130 | SCV004195620 | uncertain significance | Endometrial carcinoma | 2023-08-03 | criteria provided, single submitter | clinical testing |