Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000204672 | SCV000260127 | uncertain significance | Lynch syndrome | 2015-08-25 | criteria provided, single submitter | clinical testing | This sequence change is a tandem duplication of 85 nucleotides in exon 9 of the MSH6 mRNA (c.3969_4001+52dup). This duplication includes the 3' end of exon 9. The impact of this duplication on both MSH6 mRNA processing and protein function is unknown. This variant is not present in population databases and has not been reported in the literature. Algorithms developed to predict the effect of nucleotide changes on mRNA splicing suggest that while this duplication is not predicted to alter the consensus splice site in intron 9, it is predicted to create 2 novel splice sites downstream of the consensus splice site that if used, will create premature translation stop codon that resulting in a truncated MSH6 protein. In the absence of transcriptional studies, it is not known if these additional site actually impact MSH6 mRNA. In summary, this is a novel variant with uncertain impact on splicing. It has been classified as a Variant of Uncertain Significance. |
Color Diagnostics, |
RCV000771271 | SCV000903402 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-02-09 | criteria provided, single submitter | clinical testing | This variant creates an in-tandem duplication, encompassing the last 33 nucleotides of exon 9 and the first 52 nucleotides of intron 9 in the MSH6 gene. While this duplication does not directly disrupt the coding sequence of this gene, it creates a duplicate intron 9 splice donor site. To our knowledge, functional studies have not been reported for this variant. A similar duplication (c.3969_4001+51dup) has been reported in an individual affected with colorectal cancer whose tumor exhibited mismatch repair deficient characteristics (PMID: 14871975). 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. |
Ambry Genetics | RCV000771271 | SCV002623061 | likely benign | Hereditary cancer-predisposing syndrome | 2020-12-18 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
Labcorp Genetics |
RCV002517373 | SCV002940988 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2015-08-25 | criteria provided, single submitter | clinical testing | In summary, this is a novel variant with uncertain impact on splicing. It has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of nucleotide changes on mRNA splicing suggest that while this duplication is not predicted to alter the consensus splice site in intron 9, it is predicted to create 2 novel splice sites downstream of the consensus splice site that if used, will create premature translation stop codon that resulting in a truncated MSH6 protein. In the absence of transcriptional studies, it is not known if these additional site actually impact MSH6 mRNA. This variant is not present in population databases and has not been reported in the literature. This sequence change is a tandem duplication of 85 nucleotides in exon 9 of the MSH6 mRNA (c.3969_4001+52dup). This duplication includes the 3' end of exon 9. The impact of this duplication on both MSH6 mRNA processing and protein function is unknown. |