ClinVar Miner

Submissions for variant NM_057176.3(BSND):c.859G>T (p.Glu287Ter) (rs376784896)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000778246 SCV000914417 uncertain significance Bartter syndrome type 4 2018-12-15 criteria provided, single submitter clinical testing This variant is a stop-gained variant, which was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018) and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score for this variant, it could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change. No publications were found based on this search. This variant is located in the last exon or in the last 50 bp of the penultimate exon and may escape nonsense-mediated decay. Due to the potential impact of stop-gained variants and the lack of clarifying evidence, this variant is classified as a variant of unknown significance but suspicious for pathogenicity for this disease.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000616285 SCV000712304 uncertain significance not specified 2016-06-28 criteria provided, single submitter clinical testing The p.Glu287X variant in BSND has not been previously reported in individuals wi th hearing loss or Bartter syndrome, but has been identified in 1/66718 European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitu te.org; dbSNP rs376784896). Although this variant has been seen in the general p opulation, its frequency is not high enough to rule out a pathogenic role. This nonsense variant leads to a premature termination codon at position 287. This al teration occurs within the last exon and is likely to escape nonsense mediated d ecay (NMD) and to result in a truncated product 10% shorter than the normal prot ein. It is unclear whether the truncation impacts the protein function. In summa ry, the clinical significance of the p.Glu287X variant is uncertain.

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