Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000538201 | SCV000625300 | benign | Hereditary nonpolyposis colorectal neoplasms | 2023-11-24 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV000562322 | SCV000669849 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-08-27 | criteria provided, single submitter | clinical testing | The p.K6E variant (also known as c.16A>G), located in coding exon 1 of the MSH2 gene, results from an A to G substitution at nucleotide position 16. The lysine at codon 6 is replaced by glutamic acid, an amino acid with similar properties. This alteration was identified in 1/1358 non-cancer control individuals and in 0/57 cases, in a study looking at cancer predisposition mutations in patients with cutaneous melanoma and a history of at least two additional non-cutaneous melanoma primary cancers (Pritchard AL et al. PLoS One, 2018 Apr;13:e0194098). 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. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000759824 | SCV000889423 | uncertain significance | not provided | 2018-05-08 | criteria provided, single submitter | clinical testing | |
| Color Diagnostics, |
RCV000562322 | SCV001356213 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-08-09 | criteria provided, single submitter | clinical testing | This missense variant replaces lysine with glutamic acid at codon 6 of the MSH2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). This variant does not impact MSH2 function in a 6-thioguanine sensitivity assay in haploid human cells (internally defined LOF score threshold <= -1.32, PMID: 33357406). This variant has been reported in an individual affected with breast cancer (PMID: 33471991), as well as healthy individuals (PMID: 29641532, 33471991). This variant has been identified in 1/221766 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. |
| Sema4, |
RCV000562322 | SCV002534398 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-12-09 | criteria provided, single submitter | curation | |
| All of Us Research Program, |
RCV004003738 | SCV004826238 | uncertain significance | Lynch syndrome | 2023-08-23 | criteria provided, single submitter | clinical testing | This missense variant replaces lysine with glutamic acid at codon 6 of the MSH2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). This variant does not impact MSH2 function in a 6-thioguanine sensitivity assay in haploid human cells (internally defined LOF score threshold <= -1.32, PMID: 33357406). This variant has been reported in an individual affected with breast cancer (PMID: 33471991), as well as healthy individuals (PMID: 29641532, 33471991). This variant has been identified in 1/221766 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. |