Submissions for variant NM_000249.4(MLH1):c.832del (p.Thr278fs)

dbSNP: rs1064794122

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000484821	SCV000567896	pathogenic	not provided	2015-09-10	criteria provided, single submitter	clinical testing	This deletion of one nucleotide in MLH1 is denoted c.832delA at the cDNA level and p.Thr278GlnfsX19 (T278QfsX19) at the protein level. The normal sequence, with the base that is deleted in braces, is AGAA[A]CAGT. The deletion causes a frameshift, which changes a Threonine to a Glutamine at codon 278, and creates a premature stop codon at position 19 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. we consider this variant to be pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000484821	SCV002774358	pathogenic	not provided	2021-08-24	criteria provided, single submitter	clinical testing	This frameshift variant causes the premature termination of MLH1 protein synthesis. In addition, it was identified as a somatic variant in an MSI-positive tumor found within the colon ascendens (PMID: 24333619 (2014)). Based on the available information, this variant is classified as pathogenic.
Myriad Genetics, Inc.	RCV003449199	SCV004189959	pathogenic	Colorectal cancer, hereditary nonpolyposis, type 2	2023-07-18	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.