ClinVar Miner

Submissions for variant NM_003482.4(KMT2D):c.5267G>A (p.Arg1756Gln)

dbSNP: rs908795312
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV000768005 SCV000898784 uncertain significance Kabuki syndrome 1 2018-10-29 criteria provided, single submitter clinical testing KMT2D NM_003482.3 exon 22 p.Arg1756Gln (c.5267G>A): This variant has not been reported in the literature and is not present in large control databases. Evolutionary conservation suggests that this variant may impact the protein; computational predictive tools for this variant are unclear. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV003224413 SCV003920123 uncertain significance Kabuki syndrome 1; Choanal atresia-athelia-hypothyroidism-delayed puberty-short stature syndrome 2021-03-30 criteria provided, single submitter clinical testing KMT2D NM_003482.3 exon 22 p.Arg1756Gln (c.5267G>A): This variant has not been reported in the literature and is not present in large control databases. Evolutionary conservation suggests that this variant may impact the protein; computational predictive tools for this variant are unclear. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Labcorp Genetics (formerly Invitae), Labcorp RCV003588677 SCV004279747 uncertain significance Kabuki syndrome 2024-01-21 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1756 of the KMT2D protein (p.Arg1756Gln). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with KMT2D-related conditions. ClinVar contains an entry for this variant (Variation ID: 625967). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on KMT2D protein function. 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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