Submissions for variant NM_000336.3(SCNN1B):c.1706C>T (p.Ala569Val)

gnomAD frequency: 0.00051  dbSNP: rs140927806

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000220161	SCV000272421	uncertain significance	not specified	2017-03-20	criteria provided, single submitter	clinical testing	The p.Ala569Val variant in SCNN1B has been identified by our laboratory in one i ndividual with bronchiectasis. This variant has been identified in 0.1% (69/6637 8) of European chromosomes by the Exome Aggregation Consortium (ExAC, http://exa c.broadinstitute.org; dbSNP rs140927806). This variant has also been reported in ClinVar (Variant ID:229239). Computational prediction tools and conservation a nalysis do not provide strong support for or against an impact to the protein. I n summary, the clinical significance of the p.Ala569Val variant is uncertain.
Illumina Laboratory Services, Illumina	RCV000344774	SCV000395917	uncertain significance	Pseudohypoaldosteronism, type IB1, autosomal recessive	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, this variant 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 (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services, Illumina	RCV000402338	SCV000395918	benign	Liddle syndrome 1	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.
Illumina Laboratory Services, Illumina	RCV000305202	SCV000395919	benign	Bronchiectasis with or without elevated sweat chloride 1	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	RCV000901498	SCV001045872	benign	not provided	2023-12-22	criteria provided, single submitter	clinical testing
Johns Hopkins Genomics, Johns Hopkins University	RCV000402338	SCV001433657	likely benign	Liddle syndrome 1	2019-12-20	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003937856	SCV004752369	likely benign	SCNN1B-related disorder	2022-12-08	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).