Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
International Society for Gastrointestinal Hereditary Tumours |
RCV000075187 | SCV000106179 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation resulting in a stop codon |
Gene |
RCV000485642 | SCV000566070 | pathogenic | not provided | 2018-11-01 | criteria provided, single submitter | clinical testing | This deletion of one nucleotide in MLH1 is denoted c.1398delC at the cDNA level and p.Ser467AlafsX24 (S467AfsX24) at the protein level. The normal sequence, with the base that is deleted in brackets, is CTTC[delC]AGCA. The deletion causes a frameshift, which changes a Serine to an Alanine at codon 467, and creates a premature stop codon at position 24 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. MLH1 c.1398delC, previously published as 466delC, has been reported in a family meeting Amsterdam criteria for Lynch syndrome (Wagner 2003). We also consider this deletion to be pathogenic. |
Invitae | RCV001854290 | SCV002245945 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2022-08-07 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 89713). For these reasons, this variant has been classified as Pathogenic. This variant is also known as 466delC. This premature translational stop signal has been observed in individual(s) with Lynch syndrome (PMID: 12658575). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ser467Alafs*24) 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). |
Ambry Genetics | RCV002390215 | SCV002697689 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-08-11 | criteria provided, single submitter | clinical testing | The c.1398delC pathogenic mutation, located in coding exon 12 of the MLH1 gene, results from a deletion of one nucleotide at nucleotide position 1398, causing a translational frameshift with a predicted alternate stop codon (p.S467Afs*24). 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, |
RCV003451023 | SCV004190032 | pathogenic | Colorectal cancer, hereditary nonpolyposis, type 2 | 2023-07-20 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |