Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV004018076 | SCV004847655 | likely pathogenic | Lynch syndrome | 2019-03-18 | criteria provided, single submitter | clinical testing | The c.885-1G>T variant in MLH1 has not been previously reported in individuals with Lynch syndrome or large population studies. This variant occurs within the canonical splice site (+/- 1,2) and is predicted to cause altered splicing leading to an abnormal or absent protein. Please note, splicing tools predicted a cryptic splice site five nucleotide downstream which, if used, would result in a frameshift variant. Loss of function of the MLH1 gene is an established disease mechanism in autosomal dominant Lynch syndrome. In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely pathogenic for autosomal dominant Lynch syndrome. ACMG/AMP Criteria applied: PVS1, PM2. |