ClinVar Miner

Submissions for variant NM_001258271.1(MLH1):c.1896+1279_1896+1281del (rs1553664506)

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Total submissions: 2
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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,Sinai Health System RCV000500061 SCV000592439 likely pathogenic Lynch syndrome no assertion criteria provided clinical testing Review this variant with Melyssa Aronson before sign out - Delegate to JLE

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