Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
International Society for Gastrointestinal Hereditary Tumours |
RCV000075276 | SCV000106270 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation resulting in a stop codon |
Invitae | RCV000545817 | SCV000625083 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2023-06-05 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 89802). This premature translational stop signal has been observed in individual(s) with clinical features of Lynch syndrome (PMID: 22883484). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Trp538*) 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 | RCV000567360 | SCV000669624 | pathogenic | Hereditary cancer-predisposing syndrome | 2017-08-21 | criteria provided, single submitter | clinical testing | The p.W538* pathogenic mutation (also known as c.1613G>A), located in coding exon 14 of the MLH1 gene, results from a G to A substitution at nucleotide position 1613. This changes the amino acid from a tryptophan to a stop codon within coding exon 14. This mutation was reported in an individual with a history of colorectal, bladder and renal pelvis cancer. The renal pelvis tumor demonstrated microsatellite instability and absence of MLH1 on immunohistochemistry (Skeldon SC et al. Eur. Urol. 2013 Feb;63:379-85). 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. |
Myriad Genetics, |
RCV003451040 | SCV004190061 | 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 termination codon and is predicted to result in premature protein truncation. |