ClinVar Miner

Submissions for variant NM_181458.4(PAX3):c.142G>C (p.Gly48Arg)

dbSNP: rs1419548558
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory of Human Genetics, Universidade de São Paulo RCV000626396 SCV000678731 likely pathogenic Waardenburg syndrome type 1 2017-03-01 criteria provided, single submitter research
Center for Human Genetics, Inc, Center for Human Genetics, Inc RCV000626396 SCV000782199 pathogenic Waardenburg syndrome type 1 2016-11-01 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001853832 SCV002175904 pathogenic not provided 2023-11-27 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 48 of the PAX3 protein (p.Gly48Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with Waardenburg syndrome (PMID: 8845842, 29407415). ClinVar contains an entry for this variant (Variation ID: 488038). 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 PAX3 protein function with a positive predictive value of 95%. This variant disrupts the p.Gly48 amino acid residue in PAX3. Other variant(s) that disrupt this residue have been observed in individuals with PAX3-related conditions (PMID: 8845842, 23512835, 29407415), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.

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