ClinVar Miner

Submissions for variant NM_181458.4(PAX3):c.808C>T (p.Arg270Cys)

gnomAD frequency: 0.00001  dbSNP: rs1228590199
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Total submissions: 3
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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 RCV000660217 SCV000782217 pathogenic Waardenburg syndrome type 1 2016-11-01 criteria provided, single submitter clinical testing
GeneDx RCV002222584 SCV002499951 likely pathogenic not provided 2023-01-24 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 27013732, 25533962, 30936914, 28135719, 9654197, 31785789, 8589691, 20478267, 35607853)
Invitae RCV002222584 SCV003524925 pathogenic not provided 2022-04-13 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg270 amino acid residue in PAX3. Other variant(s) that disrupt this residue have been observed in individuals with PAX3-related conditions (PMID: 9279758, 30936914), which suggests that this may be a clinically significant amino acid residue. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 547747). This missense change has been observed in individuals with Waardenburg syndrome (PMID: 858969, 8845842, 20478267, 30936914). It has also been observed to segregate with disease in related individuals. This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 270 of the PAX3 protein (p.Arg270Cys). This variant is present in population databases (no rsID available, gnomAD 0.007%).

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