Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001025597 | SCV001187818 | pathogenic | Hereditary cancer-predisposing syndrome | 2019-02-19 | criteria provided, single submitter | clinical testing | The c.673dupA pathogenic mutation, located in coding exon 8 of the MLH1 gene, results from a duplication of A at nucleotide position 673, causing a translational frameshift with a predicted alternate stop codon (p.S225Kfs*10). This mutation has been reported in one British HNPCC family (Taylor CF et al. Hum Mutat. 2003 Dec;22(6):428-33). 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. This nucleotide position is highly conserved in available vertebrate species. |
Mayo Clinic Laboratories, |
RCV001507619 | SCV001713274 | likely pathogenic | not provided | 2020-11-23 | criteria provided, single submitter | clinical testing | PVS1, PM2 |
Invitae | RCV001862335 | SCV002143439 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2024-01-09 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Ser225Lysfs*10) 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: 14635101). ClinVar contains an entry for this variant (Variation ID: 826590). For these reasons, this variant has been classified as Pathogenic. |
Myriad Genetics, |
RCV003455133 | SCV004189862 | pathogenic | Colorectal cancer, hereditary nonpolyposis, type 2 | 2023-07-17 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |