Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000470045 | SCV000551135 | likely benign | Hereditary nonpolyposis colorectal neoplasms | 2024-01-21 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV000491796 | SCV000580255 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-08-05 | criteria provided, single submitter | clinical testing | The p.P673A variant (also known as c.2017C>G), located in coding exon 4 of the MSH6 gene, results from a C to G substitution at nucleotide position 2017. The proline at codon 673 is replaced by alanine, an amino acid with highly similar properties. In one study, this variant was detected in 0/165 colorectal cancer and/or polyposis patients and was identified in 1/2512 control individuals from a healthy population database (Rosenthal EA et al. Hum Genet, 2018 Oct;137:795-806). This variant was also 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, 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, |
RCV000491796 | SCV000685248 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-04-17 | criteria provided, single submitter | clinical testing | This missense variant replaces proline with alanine at codon 673 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 breast cancer (PMID: 33471991). This variant has been identified in 4/282320 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 |
RCV001565312 | SCV001788638 | uncertain significance | not provided | 2021-11-16 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek 2016); 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: 23621914, 17531815, 21120944) |
Sema4, |
RCV000491796 | SCV002535691 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-03-05 | criteria provided, single submitter | curation | |
Baylor Genetics | RCV003463933 | SCV004195618 | uncertain significance | Endometrial carcinoma | 2023-08-03 | criteria provided, single submitter | clinical testing | |
All of Us Research Program, |
RCV004001833 | SCV004838292 | uncertain significance | Lynch syndrome | 2023-10-30 | criteria provided, single submitter | clinical testing | This missense variant replaces proline with alanine at codon 673 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 breast cancer (PMID: 33471991). This variant has been identified in 4/282320 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. |