Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000130995 | SCV000185918 | pathogenic | Hereditary cancer-predisposing syndrome | 2012-08-14 | criteria provided, single submitter | clinical testing | 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, |
RCV002298481 | SCV002598586 | likely pathogenic | Hereditary nonpolyposis colon cancer | 2022-09-16 | criteria provided, single submitter | clinical testing | Variant summary: MLH1 c.984_997del14 (p.His329AlafsX28) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the 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. The variant was absent in 251388 control chromosomes. c.984_997del14 has been reported in the literature in an individual who underwent hereditary cancer multigene panel testing (LaDuca_2014). This report does not provide unequivocal conclusions about association of the variant with Lynch Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic. |