ClinVar Miner

Submissions for variant NM_001127701.1(SERPINA1):c.839A>T (p.Asp280Val) (rs121912714)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CSER_CC_NCGL; University of Washington Medical Center RCV000148876 SCV000190620 likely pathogenic Alpha-1-antitrypsin deficiency 2014-06-01 no assertion criteria provided research
Counsyl RCV000148876 SCV000485285 likely pathogenic Alpha-1-antitrypsin deficiency 2016-03-09 criteria provided, single submitter clinical testing
Department of Laboratory Medicine and Genetics,Trillium Health Partners Credit Valley Hospital RCV000148876 SCV000608329 pathogenic Alpha-1-antitrypsin deficiency 2014-12-08 no assertion criteria provided curation
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000398063 SCV000342428 other not provided 2016-06-22 criteria provided, single submitter clinical testing
Invitae RCV000148876 SCV000948693 pathogenic Alpha-1-antitrypsin deficiency 2018-10-12 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with valine at codon 280 of the SERPINA1 protein (p.Asp280Val). The aspartic acid residue is weakly conserved and there is a large physicochemical difference between aspartic acid and valine. This variant is present in population databases (rs121912714, ExAC 0.07%). This variant, also referred to as PI*Lowell allele, PI*Duarte allele, or PI*Null Cardiff allele, has been observed to segregate with alpha-1 antitrypsin deficiency (AATD) in families (PMID: 2240842, 2831367), and has been observed in individuals affected with AATD (PMID: 8364590, 27296815, 26321041, 17906067, 15744045, 2787118). This variant is also known as p.Asp256Val in the literature. ClinVar contains an entry for this variant (Variation ID: 17975). Experimental studies have shown that this missense change disrupts protein folding and reduces secretion of alpha-1 antitrypsin due to intracellular degradation (PMID: 2240842, 14767073,15949707). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000019576 SCV000039873 other PI P(LOWELL) 2016-07-15 no assertion criteria provided literature only
OMIM RCV000019577 SCV000039874 other PI NULL(CARDIFF) 2016-07-15 no assertion criteria provided literature only
OMIM RCV000019578 SCV000039875 other PI Q0(CARDIFF) 2016-07-15 no assertion criteria provided literature only
OMIM RCV000019605 SCV000039903 other PI P(DUARTE) 2016-07-15 no assertion criteria provided literature only

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