ClinVar Miner

Submissions for variant NM_001040108.2(MLH3):c.3475G>C (p.Asp1159His)

dbSNP: rs755836944
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Baylor Genetics RCV001292780 SCV001481430 uncertain significance Colorectal cancer, hereditary nonpolyposis, type 7 2019-02-25 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Ambry Genetics RCV004035596 SCV002613950 uncertain significance not specified 2024-11-22 criteria provided, single submitter clinical testing The p.D1159H variant (also known as c.3475G>C), located in coding exon 4 of the MLH3 gene, results from a G to C substitution at nucleotide position 3475. The aspartic acid at codon 1159 is replaced by histidine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV001292780 SCV002997435 uncertain significance Colorectal cancer, hereditary nonpolyposis, type 7 2024-03-20 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 1159 of the MLH3 protein (p.Asp1159His). This variant is present in population databases (no rsID available, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with MLH3-related conditions. ClinVar contains an entry for this variant (Variation ID: 997548). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.
Fulgent Genetics, Fulgent Genetics RCV005012729 SCV005635761 uncertain significance Endometrial carcinoma; Colorectal cancer, hereditary nonpolyposis, type 7; Colorectal cancer 2024-06-21 criteria provided, single submitter clinical testing

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