ClinVar Miner

Submissions for variant NM_181458.4(PAX3):c.811C>T (p.Arg271Cys)

dbSNP: rs1380858784
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Human Genetics, Inc, Center for Human Genetics, Inc RCV000660218 SCV000782218 pathogenic Waardenburg syndrome type 1 2016-11-01 criteria provided, single submitter clinical testing
Genetic Testing Center for Deafness, Department of Otolaryngology Head & Neck Surgery, Institute of Otolaryngology, Chinese PLA General Hospital RCV000660218 SCV001478203 pathogenic Waardenburg syndrome type 1 2019-01-01 criteria provided, single submitter clinical testing
Baylor Genetics RCV000660218 SCV001520004 pathogenic Waardenburg syndrome type 1 2019-12-06 criteria provided, single submitter clinical testing This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
Labcorp Genetics (formerly Invitae), Labcorp RCV001861717 SCV002241278 pathogenic not provided 2024-06-16 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 271 of the PAX3 protein (p.Arg271Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with autosomal dominate Waardenburg syndrome (PMID: 8589691, 8799378, 9654197, 20199465). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 547748). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on PAX3 protein function. This variant disrupts the p.Arg271 amino acid residue in PAX3. Other variant(s) that disrupt this residue have been observed in individuals with PAX3-related conditions (PMID: 8589691, 9654197), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
Center for Statistical Genetics, Columbia University RCV004808837 SCV005431520 pathogenic Waardenburg syndrome 2024-11-08 criteria provided, single submitter research

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