Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
International Society for Gastrointestinal Hereditary Tumours |
RCV000075288 | SCV000106281 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation resulting in a stop codon |
Ambry Genetics | RCV002399439 | SCV002709349 | pathogenic | Hereditary cancer-predisposing syndrome | 2018-10-09 | criteria provided, single submitter | clinical testing | The p.L547* pathogenic mutation (also known as c.1640T>A), located in coding exon 14 of the MLH1 gene, results from a T to A substitution at nucleotide position 1640. This changes the amino acid from a leucine to a stop codon within coding exon 14. In a study of 1,721 German probands suspected of HNPCC, this mutation was detected in one family (Mangold E et al. Int. J. Cancer 2005 Sep;116:692-702). 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 | RCV002514340 | SCV003525131 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2022-07-14 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 89814). This premature translational stop signal has been observed in individual(s) with Lynch syndrome (PMID: 10323887, 15849733). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Leu547*) 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). |