Submissions for variant NM_000295.5(SERPINA1):c.43C>T (p.Leu15=)

gnomAD frequency: 0.00064  dbSNP: rs147283849

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000364791	SCV000342101	uncertain significance	not provided	2017-09-29	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000377547	SCV000389662	uncertain significance	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, 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.
Invitae	RCV000377547	SCV000754981	likely benign	Alpha-1-antitrypsin deficiency	2024-01-28	criteria provided, single submitter	clinical testing
GeneDx	RCV000364791	SCV001780002	uncertain significance	not provided	2021-04-23	criteria provided, single submitter	clinical testing	In silico analysis supports that this variant does not alter splicing; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics	RCV003165759	SCV003853783	likely benign	Inborn genetic diseases	2022-12-04	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: 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.
PreventionGenetics, part of Exact Sciences	RCV003910009	SCV004721888	likely benign	SERPINA1-related condition	2019-03-14	criteria provided, single submitter	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).