Submissions for variant NM_001040108.2(MLH3):c.2411G>A (p.Cys804Tyr)

dbSNP: rs2139563242

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001987340	SCV002214248	uncertain significance	Colorectal cancer, hereditary nonpolyposis, type 7	2021-01-16	criteria provided, single submitter	clinical testing	In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The tyrosine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with MLH3-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces cysteine with tyrosine at codon 804 of the MLH3 protein (p.Cys804Tyr). The cysteine residue is weakly conserved and there is a large physicochemical difference between cysteine and tyrosine.