Submissions for variant NM_000295.5(SERPINA1):c.866dup (p.Asn289fs)

dbSNP: rs1555368557

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
HerediLab, Inc.	RCV000508966	SCV000605934	pathogenic	Alpha-1-antitrypsin deficiency	2017-01-12	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003409721	SCV004107616	likely pathogenic	SERPINA1-related condition	2023-05-26	criteria provided, single submitter	clinical testing	The SERPINA1 c.866dupA variant is predicted to result in a frameshift and premature protein termination (p.Asn289Lysfs*2). To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Frameshift variants in SERPINA1 are expected to be pathogenic. This variant is interpreted as likely pathogenic.
Baylor Genetics	RCV000508966	SCV004203114	likely pathogenic	Alpha-1-antitrypsin deficiency	2023-10-23	criteria provided, single submitter	clinical testing
Invitae	RCV000508966	SCV004664507	pathogenic	Alpha-1-antitrypsin deficiency	2023-10-29	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Asn289Lysfs*2) in the SERPINA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SERPINA1 are known to be pathogenic (PMID: 25425243). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with SERPINA1-related conditions (PMID: 36367950). This variant is also known as QO Higuey. ClinVar contains an entry for this variant (Variation ID: 440499). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.