Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
International Society for Gastrointestinal Hereditary Tumours |
RCV000075146 | SCV000106137 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation resulting in a stop codon |
Invitae | RCV001383026 | SCV001582034 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2020-05-20 | criteria provided, single submitter | clinical testing | Loss-of-function variants in MLH1 are known to be pathogenic (PMID: 15713769, 24362816). For these reasons, this variant has been classified as Pathogenic. This variant has been observed in individual(s) with Lynch syndrome (PMID: 15872200). ClinVar contains an entry for this variant (Variation ID: 89674). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Gln398*) in the MLH1 gene. It is expected to result in an absent or disrupted protein product. |
Ambry Genetics | RCV002336222 | SCV002640842 | pathogenic | Hereditary cancer-predisposing syndrome | 2020-06-29 | criteria provided, single submitter | clinical testing | The p.Q398* pathogenic mutation (also known as c.1192C>T), located in coding exon 12 of the MLH1 gene, results from a C to T substitution at nucleotide position 1192. This changes the amino acid from a glutamine to a stop codon within coding exon 12. This variant has been reported in one male diagnosed with MSI-H rectosigmoid cancer at age 49; this tumor showed loss of PMS2 and loss of MSH6 on immunohistochemistry (IHC) (Hampel H et al. N. Engl. J. Med., 2005 May;352:1851-60). It has also been reported in one of 618 unselected Chinese individuals diagnosed with colorectal cancer undergoing a 73-gene panel test (Gong R et al. Cancer Manag Res, 2019 Apr;11:3721-3739). 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, |
RCV003451011 | SCV004189905 | pathogenic | Colorectal cancer, hereditary nonpolyposis, type 2 | 2023-07-19 | 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. |