ClinVar Miner

Submissions for variant NM_002449.5(MSX2):c.572A>G (p.Gln191Arg)

dbSNP: rs1760875161
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV003759049 SCV004394210 uncertain significance Cranium bifidum occultum 2023-06-14 criteria provided, single submitter clinical testing 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. 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 MSX2 protein function. ClinVar contains an entry for this variant (Variation ID: 1050430). This variant has not been reported in the literature in individuals affected with MSX2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 191 of the MSX2 protein (p.Gln191Arg).
Department of Pathology and Laboratory Medicine, Sinai Health System RCV001357858 SCV001553448 uncertain significance not provided no assertion criteria provided clinical testing The MSX2 p.Q191R variant was not identified in the literature nor was it identified in dbSNP, ClinVar or in the following control databases: the 1000 Genomes Project, the NHLBI GO Exome Sequencing Project, or the Genome Aggregation Database (March 6, 2019, v2.1.1). The p.Q191 residue is conserved in mammals and more distantly related organisms and computational analyses (MUT Assesor, SIFT, MutationTaster, Revel, FATHMM, MetaLR, DANN) suggest that the variant may impact the protein; however, this information is not predictive enough to assume pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (Splice AI exome) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.

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