ClinVar Miner

Submissions for variant NM_002448.3(MSX1):c.655T>C (p.Trp219Arg)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002993706 SCV003290287 uncertain significance Hypoplastic enamel-onycholysis-hypohidrosis syndrome 2022-07-13 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals affected with MSX1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tryptophan, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 219 of the MSX1 protein (p.Trp219Arg). 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. 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.
GeneDx RCV003332395 SCV004040302 uncertain significance not provided 2023-03-28 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 35599849)
Center of Excellence in Genomics and Precision Dentistry, Faculty of Dentistry, Chulalongkorn University RCV004794601 SCV005407771 likely pathogenic Tooth agenesis, selective, 1 criteria provided, single submitter clinical testing A heterozygous missense variant, c.655T>C (p.Trp219Arg), in the MSX1 gene was identified in a patient with tooth agenesis and her affected mother through exome sequencing. This variant was absent in population databases, including gnomAD, TOPMed, GenomeAsia, and an in-house database of Thai exomes. A change at the same amino acid position, p.Trp219Cys in MSX1, was previously reported in non-syndromic tooth agenesis patients (Keskin et al., 2021; PMID: 33725141). Based on ACMG Guidelines for variant interpretation and classification, the p.Trp219Arg variant was classified as likely pathogenic.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.