ClinVar Miner

Submissions for variant NM_001122659.3(EDNRB):c.1285G>A (p.Gly429Arg)

gnomAD frequency: 0.00022  dbSNP: rs144565124
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000220584 SCV000271757 uncertain significance not specified 2015-08-11 criteria provided, single submitter clinical testing The p.Gly519Arg variant in EDNRB has not been previously reported in individuals with hearing loss or Waardenburg syndrome, but has been identified in 6/65674 E uropean chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broad institute.org; dbSNP rs144565124). Although this variant has been seen in the ge neral population, its frequency is not high enough to rule out a pathogenic role . Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. In summary, the clinical signi ficance of the Gly519Arg variant is uncertain.
Illumina Laboratory Services, Illumina RCV000402655 SCV000384802 uncertain significance Waardenburg syndrome 2016-06-14 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000310434 SCV000384803 uncertain significance Hirschsprung Disease, Recessive 2016-06-14 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000220584 SCV001362333 uncertain significance not specified 2019-01-23 criteria provided, single submitter clinical testing Variant summary: EDNRB c.1285G>A (p.Gly429Arg) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00014 in 275528 control chromosomes (gnomAD). To our knowledge, no occurrence of c.1285G>A in individuals affected with Waardenburg syndrome type 4A and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and both laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Invitae RCV001853450 SCV002311646 uncertain significance not provided 2023-10-04 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 429 of the EDNRB protein (p.Gly429Arg). This variant is present in population databases (rs144565124, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with EDNRB-related conditions. ClinVar contains an entry for this variant (Variation ID: 228662). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.
Fulgent Genetics, Fulgent Genetics RCV002478768 SCV002788065 uncertain significance ABCD syndrome; Hirschsprung disease, susceptibility to, 2; Waardenburg syndrome type 4A 2022-03-08 criteria provided, single submitter clinical testing
Ambry Genetics RCV002517548 SCV003737828 uncertain significance Inborn genetic diseases 2022-10-26 criteria provided, single submitter clinical testing The c.1285G>A (p.G429R) alteration is located in exon 8 (coding exon 7) of the EDNRB gene. This alteration results from a G to A substitution at nucleotide position 1285, causing the glycine (G) at amino acid position 429 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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