ClinVar Miner

Submissions for variant NM_170606.3(KMT2C):c.4602G>T (p.Gln1534His)

dbSNP: rs992987667
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Breda Genetics srl RCV001725873 SCV001962687 uncertain significance Kleefstra syndrome 2 2021-02-03 criteria provided, single submitter clinical testing Based on allele frequency, in-silico prediction scores and a certain overlap with the clinical phenotype, we interpreted this variant at least as of uncertain significance. The lack of one or more of the following features has discouraged further investigations: lack of a possible second hit in autosomal recessive conditions, presence of healthy controls in databases for autosomal dominant conditions, presence of unmatching cardinal clinical features in the patient or in the known gene-disease association, and/or variant type outside the known gene mutational spectrum.
Mendelics RCV002246464 SCV002517252 uncertain significance not specified 2022-05-04 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003718419 SCV004517258 uncertain significance not provided 2023-12-12 criteria provided, single submitter clinical testing This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 1534 of the KMT2C protein (p.Gln1534His). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with KMT2C-related conditions. ClinVar contains an entry for this variant (Variation ID: 1299248). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt KMT2C protein function with a negative predictive value of 80%. 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.

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