Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
International Society for Gastrointestinal Hereditary Tumours |
RCV000074849 | SCV000108061 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation resulting in a stop codon |
Ambry Genetics | RCV000561009 | SCV000673950 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-10-12 | criteria provided, single submitter | clinical testing | The p.Q1146* pathogenic mutation (also known as c.3436C>T), located in coding exon 5 of the MSH6 gene, results from a C to T substitution at nucleotide position 3436. This changes the amino acid from a glutamine to a stop codon within coding exon 5. This pathogenic mutation was reported in an individual with personal and family history consistent with Muir-Torre syndrome (Mangold E et al. Br. J. Dermatol. 2007 Jan;156(1):158-62). 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. |
Invitae | RCV000629768 | SCV000750724 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2023-05-24 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Lynch syndrome (PMID: 17199584). ClinVar contains an entry for this variant (Variation ID: 89382). For these reasons, this variant has been classified as Pathogenic. This sequence change creates a premature translational stop signal (p.Gln1146*) 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). |
Gene |
RCV000657654 | SCV000779402 | pathogenic | not provided | 2017-06-14 | criteria provided, single submitter | clinical testing | This variant is denoted MSH6 c.3436C>T at the cDNA level and p.Gln1146Ter (Q1146X) at the protein level. The substitution creates a nonsense variant, which changes a Glutamine to a premature stop codon (CAG>TAG), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been reported in at least two individuals with colorectal cancer, one of whom also had a sebaceous neoplasm, and is considered pathogenic (Mangold 2007, Steinke 2008). |
Myriad Genetics, |
RCV003450966 | SCV004187411 | pathogenic | Lynch syndrome 5 | 2023-08-23 | 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. |