Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000564235 | SCV000673850 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2017-07-05 | criteria provided, single submitter | clinical testing | The c.2048_2050delTCT variant (also known as p.F683del) is located in coding exon 18 of the MLH1 gene. This variant results from an in-frame TCT deletion at nucleotide positions 2048 to 2050. This results in the in-frame deletion of a phenylalanine at codon 683. This alteration showed moderate segregation with disease in a family that met Amsterdam II criteria and two family members who tested positive for this alteration also displayed loss of MLH1 protein expression in their tumors by immunohistochemistry (Ambry internal data). Based on internal structural analysis, this alteration is part of a structured region with known function and is more destabilizing than known likely pathogenic variants in the region. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by PROVEAN in silico analysis (Choi Y et al., Bioinformatics 2015 Aug; 31(16):2745-7). Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
| Department of Pathology and Laboratory Medicine, |
RCV000500061 | SCV000592439 | likely pathogenic | Lynch syndrome | no assertion criteria provided | clinical testing | Review this variant with Melyssa Aronson before sign out - Delegate to JLE |