Total submissions: 4
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 | 2018-05-24 | 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 | 2017-12-05 | criteria provided, single submitter | clinical testing | 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. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual with suspected Lynch syndrome (PMID: 17199584). ClinVar contains an entry for this variant (Variation ID: 89382). Loss-of-function variants in MSH6 are known to be pathogenic (PMID: 18269114, 24362816). For these reasons, this variant has been classified as Pathogenic. |
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). |