Submissions for variant NM_000295.5(SERPINA1):c.774G>A (p.Lys258=)

gnomAD frequency: 0.01536  dbSNP: rs34112109

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000151832	SCV000200305	benign	not specified	2013-02-21	criteria provided, single submitter	clinical testing	Lys258Lys in exon 5 of SERPINA1: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue and is not located w ithin the splice consensus sequence. It has been identified in 4.9% (217/4406) o f African American chromosomes from a broad population by the NHLBI Exome Sequen cing Project (http://evs.gs.washington.edu/EVS; dbSNP rs34112109).
PreventionGenetics, part of Exact Sciences	RCV000151832	SCV000303524	benign	not specified		criteria provided, single submitter	clinical testing
Invitae	RCV000860964	SCV001001154	benign	Alpha-1-antitrypsin deficiency	2024-02-01	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000860964	SCV001279507	likely benign	Alpha-1-antitrypsin deficiency	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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.