Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
International Society for Gastrointestinal Hereditary Tumours |
RCV000075015 | SCV000108235 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation resulting in a stop codon |
Invitae | RCV001071476 | SCV001236783 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2022-10-09 | criteria provided, single submitter | clinical testing | This premature translational stop signal has been observed in individual(s) with Lynch syndrome (PMID: 18269114). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 89546). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Tyr214*) 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). |
Ambry Genetics | RCV003162479 | SCV003867105 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-11-23 | criteria provided, single submitter | clinical testing | The p.Y214* pathogenic mutation (also known as c.642C>A), located in coding exon 4 of the MSH6 gene, results from a C to A substitution at nucleotide position 642. This changes the amino acid from a tyrosine to a stop codon within coding exon 4. This variant has been identified in a cohort of Hereditary Non-polyposis Colorectal Cancer (HNPCC) families (Devlin LA et al. Ulster Med J, 2008 Jan;77:25-30). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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. |