Submissions for variant NM_002448.3(MSX1):c.752_753delinsAA (p.Phe251Ter)

dbSNP: rs1553878166

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000556981	SCV000634357	uncertain significance	Hypoplastic enamel-onycholysis-hypohidrosis syndrome	2016-10-31	criteria provided, single submitter	clinical testing	In summary, this is a novel truncating variant in the last exon of the MSX1 gene. While it is absent from the population and removes residues that may be important for protein function, the current evidence is insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance. An experimental study has shown that the the last 32 amino acids of the MSX1 protein are critical for DNA binding specificity, nuclear localization, and transcriptional repression (PMID: 16600910). However, the clinical significance of these effects on protein function is unknown. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a MSX1-related disease. This sequence change results in a premature translational stop signal in the last exon of the MSX1 mRNA at codon 251 (p.Phe251*). While this is not anticipated to result in nonsense mediated decay, it is expected to delete the last 52 amino acids of the MSX1 protein.