ClinVar Miner

Submissions for variant NM_000249.4(MLH1):c.1849A>G (p.Lys617Glu)

dbSNP: rs1575621757
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000821610 SCV000962375 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2018-08-07 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but 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 MLH1-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces lysine with glutamic acid at codon 617 of the MLH1 protein (p.Lys617Glu). The lysine residue is weakly conserved and there is a small physicochemical difference between lysine and glutamic acid.
Ambry Genetics RCV002408983 SCV002710578 uncertain significance Hereditary cancer-predisposing syndrome 2024-07-15 criteria provided, single submitter clinical testing The p.K617E variant (also known as c.1849A>G), located in coding exon 16 of the MLH1 gene, results from an A to G substitution at nucleotide position 1849. The lysine at codon 617 is replaced by glutamic acid, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV005036221 SCV005664472 uncertain significance Mismatch repair cancer syndrome 1; Muir-Torré syndrome; Colorectal cancer, hereditary nonpolyposis, type 2 2024-02-09 criteria provided, single submitter clinical testing

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