Total submissions: 11
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genomic Diagnostic Laboratory, |
RCV000203004 | SCV000257641 | uncertain significance | Lynch syndrome | 2015-03-06 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000219542 | SCV000279304 | uncertain significance | not provided | 2023-03-14 | 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; Observed in cases and unaffected controls from a breast cancer study (Dorling et al., 2021); This variant is associated with the following publications: (PMID: 25042771, 28912153, 17531815, 21120944, 33471991) |
Counsyl | RCV000410374 | SCV000488920 | uncertain significance | Lynch syndrome 5 | 2016-07-18 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000524152 | SCV000551047 | likely benign | Hereditary nonpolyposis colorectal neoplasms | 2023-10-04 | criteria provided, single submitter | clinical testing | |
Mendelics | RCV000203004 | SCV000837908 | uncertain significance | Lynch syndrome | 2018-07-02 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV000774606 | SCV000908408 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-05-04 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with tryptophan at codon 1034 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. This variant has not been reported in individuals affected with MSH6-related disorders in the literature. This variant has been identified in 5/278768 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. |
Ambry Genetics | RCV000774606 | SCV001179911 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-08-17 | criteria provided, single submitter | clinical testing | The p.R1034W variant (also known as c.3100C>T), located in coding exon 4 of the MSH6 gene, results from a C to T substitution at nucleotide position 3100. The arginine at codon 1034 is replaced by tryptophan, an amino acid with dissimilar properties. This alteration was seen in 1/732 breast cancer patients, 0/189 colorectal cancer patients and 0/490 cancer-free elderly controls in a Turkish population (Akcay IM et al. Int J Cancer, 2021 Jan;148:285-295). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Sema4, |
RCV000774606 | SCV002535790 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-02-27 | criteria provided, single submitter | curation | |
Laboratorio de Genetica e Diagnostico Molecular, |
RCV000410374 | SCV003806857 | uncertain significance | Lynch syndrome 5 | 2022-10-06 | criteria provided, single submitter | clinical testing | ACMG classification criteria: PM2 supporting, PP3 supporting |
Myriad Genetics, |
RCV000410374 | SCV004018924 | uncertain significance | Lynch syndrome 5 | 2023-03-28 | 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. |
All of Us Research Program, |
RCV000203004 | SCV004837113 | uncertain significance | Lynch syndrome | 2023-08-15 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with tryptophan at codon 1034 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). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 5/278768 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. |