ClinVar Miner

Submissions for variant NM_181458.4(PAX3):c.251C>T (p.Ser84Phe)

dbSNP: rs104893651
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
King Laboratory, University of Washington RCV000004433 SCV001976370 pathogenic Waardenburg syndrome type 1 2020-08-01 criteria provided, single submitter research PAX3 c.251C>T, p.S84F alters a residue of PAX3 conserved throughout all sequenced vertebrates. It has been reported multiple times as a pathogenic variant in the Palestinian population (PMID: 7726174). In our cohort, the variant was heterozygous in 16 Palestinian children and adults with features of Waardenburg syndrome from 4 extended kindreds (Abu Rayyan 2020).
Invitae RCV003555913 SCV004293985 pathogenic not provided 2023-07-18 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. 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. ClinVar contains an entry for this variant (Variation ID: 4212). This missense change has been observed in individual(s) with Waardenburg syndrome (PMID: 7726174). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 84 of the PAX3 protein (p.Ser84Phe).
OMIM RCV000004432 SCV000024605 pathogenic Waardenburg syndrome type 3 1995-05-01 no assertion criteria provided literature only
OMIM RCV000004433 SCV000024606 pathogenic Waardenburg syndrome type 1 1995-05-01 no assertion criteria provided literature only
Hereditary Research Laboratory, Bethlehem University RCV000004433 SCV000538111 pathogenic Waardenburg syndrome type 1 2016-06-04 no assertion criteria provided research Waardenburg syn

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