Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
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 | 2024-01-02 | 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, gnomAD 0.008%). Disruption of the initiator codon has been observed in individuals with Bartter syndrome (PMID: 11687798, 16773427, 24902942). ClinVar contains an entry for this variant (Variation ID: 4384). For these reasons, this variant has been classified as Pathogenic. |
Center for Genomics, |
RCV000004634 | SCV003920514 | pathogenic | Bartter disease type 4A | 2022-05-24 | criteria provided, single submitter | clinical testing | This variant is predicted to abolish the translation initiation codon, resulting in an abnormal or absent protein; loss of function is an established mechanism of disease for this gene (Janssen 2009 PMID: 18776122). Variants altering the initiation codon have been reported in the literature in the homozygous state in at least 9 individuals with Bartter syndrome (Selected publications: Birkenhäger 2001 PMID: 11687798; Zaffanello 2006 PMID: 16583241; Bettinelli 2014 PMID: 24902942). This variant is present in the Genome Aggregation Database (Highest MAF: 0.007% [5/68032] https://gnomad.broadinstitute.org/variant/1-54999189-G-A?dataset=gnomad_r3); please note, disease-causing variants may be present in control databases at low frequencies, reflective of the general population, carrier status, and/or variable expressivity. It is also present in ClinVar, with multiple laboratories classifying it as pathogenic or likely pathogenic (Variation ID: 4384). Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. In summary, this variant is classified as pathogenic. |
Gene |
RCV001057884 | SCV004168673 | pathogenic | not provided | 2023-04-06 | criteria provided, single submitter | clinical testing | Identified with a second variant (phase unknown) in a patient with Bartter syndrome and sensorineural hearing loss in published literature (Birkenhager et al., 2001); Initiation codon variant in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 31589614, 16773427, 11687798, 24902942, 19096086, 16583241) |
OMIM | RCV000004634 | SCV000024808 | pathogenic | Bartter disease type 4A | 2001-11-01 | no assertion criteria provided | literature only | |
Natera, |
RCV001272340 | SCV001454251 | pathogenic | Bartter syndrome | 2020-09-16 | no assertion criteria provided | clinical testing |