Submissions for variant NM_018979.4(WNK1):c.1855A>G (p.Thr619Ala)

gnomAD frequency: 0.00086  dbSNP: rs149388376

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000286984	SCV000381820	benign	Pseudohypoaldosteronism type 2C	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000524948	SCV000649399	likely benign	Neuropathy, hereditary sensory and autonomic, type 2A; Pseudohypoaldosteronism type 2C	2024-01-20	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001812802	SCV001470985	uncertain significance	not provided	2021-06-17	criteria provided, single submitter	clinical testing	The WNK1 c.1855A>G; p.Thr619Ala variant (rs149388376), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 310741). This variant is found in the non-Finnish European population with an overall allele frequency of 0.13% (168/128,558 alleles) in the Genome Aggregation Database. The threonine at codon 619 is moderately conserved, and computational analyses predict that this variant is neutral (REVEL: 0.078). However, due to limited information, the clinical significance of the p.Thr619Ala variant is uncertain at this time.
CeGaT Center for Human Genetics Tuebingen	RCV001812802	SCV002585368	uncertain significance	not provided	2024-07-01	criteria provided, single submitter	clinical testing	WNK1: PM2:Supporting, BP4
Ambry Genetics	RCV002411204	SCV002724036	uncertain significance	Inborn genetic diseases	2022-03-11	criteria provided, single submitter	clinical testing	The p.T619A variant (also known as c.1855A>G), located in coding exon 7 of the WNK1 gene, results from an A to G substitution at nucleotide position 1855. The threonine at codon 619 is replaced by alanine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species, and alanine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences	RCV003967906	SCV004778123	likely benign	WNK1-related disorder	2022-02-11	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).