ClinVar Miner

Submissions for variant NM_003482.4(KMT2D):c.3595C>G (p.Leu1199Val)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Fulgent Genetics, Fulgent Genetics RCV005011255 SCV005636055 uncertain significance Kabuki syndrome 1; Choanal atresia-athelia-hypothyroidism-delayed puberty-short stature syndrome 2024-04-28 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV005112555 SCV005801288 uncertain significance Kabuki syndrome 2024-03-16 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1199 of the KMT2D protein (p.Leu1199Val). 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. This missense change has been observed in at least one individual who was not affected with KMT2D-related conditions (Invitae). 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 expected to disrupt KMT2D protein function with a positive 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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