Submissions for variant NM_001127701.1(SERPINA1):c.17C>T (p.Ser6Leu)

gnomAD frequency: 0.00004  dbSNP: rs140814100

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000596635	SCV000708927	uncertain significance	not provided	2018-01-09	criteria provided, single submitter	clinical testing
Counsyl	RCV000148880	SCV000796829	uncertain significance	Alpha-1-antitrypsin deficiency	2018-01-08	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000148880	SCV002781991	uncertain significance	Alpha-1-antitrypsin deficiency	2022-02-16	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000148880	SCV004678177	uncertain significance	Alpha-1-antitrypsin deficiency	2023-12-14	criteria provided, single submitter	clinical testing	This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 6 of the SERPINA1 protein (p.Ser6Leu). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with SERPINA1-related conditions (PMID: 2227940). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as Ser(-19)Leu. ClinVar contains an entry for this variant (Variation ID: 17970). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SERPINA1 protein function with a positive predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
OMIM	RCV000019570	SCV000039867	other	PI Z(WREXHAM)	2016-07-15	no assertion criteria provided	literature only
CSER _CC_NCGL, University of Washington	RCV000148880	SCV000190624	uncertain significance	Alpha-1-antitrypsin deficiency	2014-06-01	no assertion criteria provided	research
Department of Laboratory Medicine and Genetics, Trillium Health Partners Credit Valley Hospital	RCV000148880	SCV000608303	pathogenic	Alpha-1-antitrypsin deficiency	2014-12-08	no assertion criteria provided	clinical testing