Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001322640 | SCV001513520 | uncertain significance | Hypoplastic enamel-onycholysis-hypohidrosis syndrome | 2020-08-03 | criteria provided, single submitter | clinical testing | This sequence change replaces serine with tryptophan at codon 208 of the MSX1 protein (p.Ser208Trp). The serine residue is highly conserved and there is a large physicochemical difference between serine and tryptophan. This variant is present in population databases (rs104893853, ExAC 0.003%). 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. |
Prevention |
RCV004531112 | SCV004710453 | uncertain significance | MSX1-related disorder | 2023-11-27 | no assertion criteria provided | clinical testing | The MSX1 c.623C>G variant is predicted to result in the amino acid substitution p.Ser208Trp. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0050% of alleles in individuals of East Asian descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |