Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000232271 | SCV000283815 | pathogenic | Lynch syndrome | 2015-12-28 | criteria provided, single submitter | clinical testing | This sequence change duplicates 5 nucleotides in exon 8 of the MSH6 mRNA (c.3717_3721dupAAAAT), causing a frameshift at codon 1241. This creates a premature translational stop signal (p.Cys1241*) and is expected to result in an absent or disrupted protein product. While this particular variant has not been reported in the literature, truncating variants in MSH6 are known to be pathogenic (PMID: 24362816, 18269114). For these reasons, this variant has been classified as Pathogenic. |
Invitae | RCV001386273 | SCV001586442 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2015-12-28 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. While this particular variant has not been reported in the literature, truncating variants in MSH6 are known to be pathogenic (PMID: 24362816, 18269114). This sequence change duplicates 5 nucleotides in exon 8 of the MSH6 mRNA (c.3717_3721dupAAAAT), causing a frameshift at codon 1241. This creates a premature translational stop signal (p.Cys1241*) and is expected to result in an absent or disrupted protein product. |
Ambry Genetics | RCV002347859 | SCV002623112 | pathogenic | Hereditary cancer-predisposing syndrome | 2019-07-08 | criteria provided, single submitter | clinical testing | The c.3717_3721dupAAAAT pathogenic mutation, located in coding exon 8 of the MSH6 gene, results from a duplication of AAAAT at nucleotide position 3717, causing a translational frameshift with a predicted alternate stop codon (p.C1241*). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |