Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
International Society for Gastrointestinal Hereditary Tumours |
RCV000075944 | SCV000106962 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation resulting in a stop codon |
Invitae | RCV001388084 | SCV001588931 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2022-06-11 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.His318Glnfs*49) in the MLH1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MLH1 are known to be pathogenic (PMID: 15713769, 24362816). 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: 10660333). ClinVar contains an entry for this variant (Variation ID: 90451). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. For these reasons, this variant has been classified as Pathogenic. |
Ambry Genetics | RCV002371914 | SCV002690748 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-09-27 | criteria provided, single submitter | clinical testing | The c.954delC pathogenic mutation, located in coding exon 11 of the MLH1 gene, results from a deletion of one nucleotide at nucleotide position 954, causing a translational frameshift with a predicted alternate stop codon (p.H318Qfs*49). This mutation has been reported in several individuals with HNPCC (De Lellis L et al. PLoS ONE, 2013 Nov;8:e81194; Mangold E et al. Int. J. Cancer, 2005 Sep;116:692-702; Curia MC et al. Cancer Res. 1999 Aug;59:3570-5; Panariello L et al. Hum. Mutat. 1998;12:216-7). Of note, this alteration is also designated as (codon 318 C del and p.His318fs) in published literature. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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, |
RCV003452791 | SCV004186448 | pathogenic | Colorectal cancer, hereditary nonpolyposis, type 2 | 2023-07-18 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |