Submissions for variant NM_004070.4(CLCNKA):c.1339G>A (p.Ala447Thr)

dbSNP: rs1805152

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001533981	SCV001750864	benign	not provided	2018-11-10	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 17510212)
Genome-Nilou Lab	RCV001579083	SCV001806486	benign	Bartter disease type 4B	2021-07-22	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001806232	SCV002051169	benign	not specified	2021-12-16	criteria provided, single submitter	clinical testing	Variant summary: CLCNKA c.1339G>A (p.Ala447Thr) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.55 in 250078 control chromosomes, suggesting that it is the major allele and therefore benign. The observed variant frequency is approximately 490 fold of the estimated maximal expected allele frequency for a pathogenic variant in CLCNKA causing Bartter Syndrome, Type 4b phenotype (0.0011), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.1339G>A in individuals affected with Bartter Syndrome, Type 4b 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. All laboratories classified the variant as benign. Based on the evidence outlined above, the variant was classified as benign.
Breakthrough Genomics, Breakthrough Genomics	RCV001533981	SCV005282666	benign	not provided		criteria provided, single submitter	not provided