Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
International Society for Gastrointestinal Hereditary Tumours |
RCV000074690 | SCV000107893 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation resulting in a stop codon |
Ambry Genetics | RCV002408572 | SCV002710906 | pathogenic | Hereditary cancer-predisposing syndrome | 2019-03-29 | criteria provided, single submitter | clinical testing | The p.S612* pathogenic mutation (also known as c.1835C>A), located in coding exon 4 of the MSH6 gene, results from a C to A substitution at nucleotide position 1835. This changes the amino acid from a serine to a stop codon within coding exon 4. This mutation has been detected in multiple Lynch syndrome patients whose tumors demonstrated microsatellite instability and/or loss of MSH6 protein expression on IHC (Okkels H et al. Int J Colorectal Dis. 2006 Dec;21(8):847-50; Klarskov L et al. Am J Surg Pathol. 2011 Sep;35(9):1391-9; Baert-Desurmont S et al. Eur J Hum Genet. 2018 Nov;26(11):1597-1602). In addition to the clinical data presented in the literature, 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. |
Myriad Genetics, |
RCV003450933 | SCV004185745 | pathogenic | Lynch syndrome 5 | 2023-08-15 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation. |
Invitae | RCV003593866 | SCV004293906 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2023-06-23 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 89227). This premature translational stop signal has been observed in individual(s) with colorectal cancer (PMID: 16525781). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ser612*) in the MSH6 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MSH6 are known to be pathogenic (PMID: 18269114, 24362816). |