ClinVar Miner

Submissions for variant NM_001127701.1(SERPINA1):c.194T>C (p.Leu65Pro)

gnomAD frequency: 0.00004  dbSNP: rs28931569
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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000201848 SCV000788706 likely pathogenic Alpha-1-antitrypsin deficiency 2016-12-28 criteria provided, single submitter clinical testing
Eurofins Ntd Llc (ga) RCV000729804 SCV000857495 pathogenic not provided 2017-10-17 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000201848 SCV000893355 likely pathogenic Alpha-1-antitrypsin deficiency 2022-01-19 criteria provided, single submitter clinical testing
Invitae RCV000201848 SCV000961591 pathogenic Alpha-1-antitrypsin deficiency 2024-01-04 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 65 of the SERPINA1 protein (p.Leu65Pro). This variant is present in population databases (rs28931569, gnomAD 0.009%). This missense change has been observed in individual(s) with alpha 1-antitrypsin deficiency (PMID: 3262617, 9635295). 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 M procida and p.Leu41Pro. ClinVar contains an entry for this variant (Variation ID: 17971). 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 not expected to disrupt SERPINA1 protein function with a negative predictive value of 80%. Experimental studies have shown that this missense change affects SERPINA1 function (PMID: 14767073). For these reasons, this variant has been classified as Pathogenic.
Mendelics RCV000201848 SCV001139507 likely pathogenic Alpha-1-antitrypsin deficiency 2019-05-28 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV000201848 SCV002019173 likely pathogenic Alpha-1-antitrypsin deficiency 2020-04-05 criteria provided, single submitter clinical testing
Institute of Human Genetics, University Hospital Muenster RCV001807004 SCV002054118 likely pathogenic Reduced circulating alpha-1-antitrypsin concentration 2021-12-05 criteria provided, single submitter clinical testing ACMG categories: PM1,PM2,PP3,PP5
Baylor Genetics RCV000201848 SCV004203115 likely pathogenic Alpha-1-antitrypsin deficiency 2023-10-22 criteria provided, single submitter clinical testing
OMIM RCV000019571 SCV000039868 other PI M(PROCIDA) 2016-07-15 no assertion criteria provided literature only
GeneReviews RCV000201848 SCV000256622 pathogenic Alpha-1-antitrypsin deficiency 2014-05-01 no assertion criteria provided literature only
Department of Laboratory Medicine and Genetics, Trillium Health Partners Credit Valley Hospital RCV000201848 SCV000608305 pathogenic Alpha-1-antitrypsin deficiency 2014-12-08 no assertion criteria provided curation Reduced enzyme activity

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