Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000165049 | SCV000215749 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-09-21 | criteria provided, single submitter | clinical testing | The c.4001+5C>G intronic variant results from a C to G substitution 5 nucleotides after coding exon 9 in the MSH6 gene. This nucleotide position is poorly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will not have any significant effect on splicing. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Gene |
RCV000600753 | SCV000721215 | likely benign | not specified | 2017-07-12 | criteria provided, single submitter | clinical testing | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. |
Labcorp Genetics |
RCV001352220 | SCV001546757 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2023-04-22 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 185601). This variant has not been reported in the literature in individuals affected with MSH6-related conditions. This sequence change falls in intron 9 of the MSH6 gene. It does not directly change the encoded amino acid sequence of the MSH6 protein. It affects a nucleotide within the consensus splice site. |
Color Diagnostics, |
RCV000165049 | SCV002052674 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-02-13 | criteria provided, single submitter | clinical testing | This variant causes a C to G nucleotide substitution at the +5 position of intron 9 of the MSH6 gene. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified 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. |