Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000562522 | SCV000669829 | pathogenic | Hereditary cancer-predisposing syndrome | 2024-01-05 | criteria provided, single submitter | clinical testing | The c.75delC pathogenic mutation, located in coding exon 1 of the MSH2 gene, results from a deletion of one nucleotide at nucleotide position 75, causing a translational frameshift with a predicted alternate stop codon (p.M26Cfs*38). 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. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000590325 | SCV000696281 | likely pathogenic | Lynch syndrome | 2017-05-02 | criteria provided, single submitter | clinical testing | Variant summary: The MSH2 c.75delC (p.Met26Cysfs) variant results in a premature termination codon, predicted to cause a truncated or absent MSH2 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. c.387_388delTC, p.Gln130fs). One in silico tool predicts a damaging outcome for this variant. This variant is absent in 56800 control chromosomes. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as likely pathogenic. |
Myriad Genetics, |
RCV003451251 | SCV004186971 | pathogenic | Lynch syndrome 1 | 2023-07-26 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |