ClinVar Miner

Submissions for variant NM_001040108.2(MLH3):c.2482G>T (p.Glu828Ter)

dbSNP: rs587776622
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV004018568 SCV003913812 uncertain significance not specified 2022-11-10 criteria provided, single submitter clinical testing The p.E828* variant (also known as c.2482G>T), located in coding exon 1 of the MLH3 gene, results from a G to T substitution at nucleotide position 2482. This changes the amino acid from a glutamic acid to a stop codon within coding exon 1. This variant was identified in a cohort of patients with primary prostate cancer comprised African American and European Ancestry (Kohaar I et al. Nat Commun, 2022 03;13:1361). This alteration is expected to result in protein truncation or nonsense-mediated mRNA decay. However, loss of function of MLH3 has not been established as a mechanism of disease. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV003614030 SCV004468974 uncertain significance Colorectal cancer, hereditary nonpolyposis, type 7 2023-12-28 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu828*) in the MLH3 gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in MLH3 cause disease. This variant is not present in population databases (gnomAD no frequency). 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: 5557). 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.
OMIM RCV000005896 SCV000026078 pathogenic Carcinoma of colon 2001-05-01 no assertion criteria provided literature only

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