ClinVar Miner

Submissions for variant NM_057176.3(BSND):c.3G>A (p.Met1Ile) (rs74315286)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000004634 SCV000914414 likely pathogenic Bartter disease type 4a 2018-12-18 criteria provided, single submitter clinical testing The c.3G>A (p.Met1?) variant is in the initiation codon and abolishes the transcription start site. The p.Met1? variant, (described as p.Met1Ile), is reported in three studies in which it is found in a total of four individuals with Bartter syndrome. The variant was found in a homozygous state in two individuals and in a compound heterozygous state in one other individual all with Bartter syndrome with hearing loss and in a homozygous state in a fourth individual with Bartter syndrome but for whom no further phenotype data were provided (Birkenhager et al. 2001; Zaffanello et al. 2006; Brochard et al. 2009; Bettinelli et al. 2014).). The p.Met1? variant was absent from 422 control chromosomes and is reported at a frequency of 0.000070 in the European (non-Finnish) population of the Genome Aggregation Database. Based on the evidence and the potential impact of the variant on protein translation, the p.Met1? variant is classified as likely pathogenic for Bartter syndrome. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Invitae RCV001057884 SCV001222405 pathogenic not provided 2020-07-09 criteria provided, single submitter clinical testing This sequence change affects the initiator methionine of the BSND mRNA. The next in-frame methionine is located at codon 26. This variant is present in population databases (rs74315286, ExAC 0.01%). Disruption of the initiator methionine has been observed in several individuals affected with Bartter syndrome (PMID: 11687798, 24902942, 16773427). ClinVar contains an entry for this variant (Variation ID: 4384). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000004634 SCV000024808 pathogenic Bartter disease type 4a 2001-11-01 no assertion criteria provided literature only
Natera, Inc. RCV001272340 SCV001454251 pathogenic Bartter syndrome 2020-09-16 no assertion criteria provided clinical testing

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