ClinVar Miner

Submissions for variant NM_002448.3(MSX1):c.581A>G (p.Lys194Arg)

gnomAD frequency: 0.00020  dbSNP: rs149092063
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001218812 SCV001390716 uncertain significance Hypoplastic enamel-onycholysis-hypohidrosis syndrome 2019-06-05 criteria provided, single submitter clinical testing This sequence change replaces lysine with arginine at codon 194 of the MSX1 protein (p.Lys194Arg). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and arginine. This variant is present in population databases (rs149092063, ExAC 0.02%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has not been reported in the literature in individuals with MSX1-related conditions. 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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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