Submissions for variant NM_000295.5(SERPINA1):c.424C>T (p.Leu142=)

gnomAD frequency: 0.03085  dbSNP: rs20546

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000155575	SCV000205277	benign	not specified	2013-02-21	criteria provided, single submitter	clinical testing	Leu142Leu in exon 4 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 2.4% (204/8600) o f European American chromosomes from a broad population by the NHLBI Exome Seque ncing Project (http://evs.gs.washington.edu/EVS; dbSNP rs20546).
PreventionGenetics, part of Exact Sciences	RCV000155575	SCV000303521	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000405780	SCV000389654	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 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	RCV000405780	SCV000630390	benign	Alpha-1-antitrypsin deficiency	2024-02-01	criteria provided, single submitter	clinical testing
GeneDx	RCV001689704	SCV001913367	benign	not provided	2018-07-09	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002326886	SCV002628680	benign	Inborn genetic diseases	2017-11-28	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000155575	SCV003928922	benign	not specified	2023-04-17	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV001689704	SCV005293376	benign	not provided		criteria provided, single submitter	not provided
Department of Laboratory Medicine and Genetics, Trillium Health Partners Credit Valley Hospital	RCV000405780	SCV000608316	benign	Alpha-1-antitrypsin deficiency	2014-12-08	no assertion criteria provided	clinical testing