ClinVar Miner

Submissions for variant NM_001127701.1(SERPINA1):c.194T>C (p.Leu65Pro) (rs28931569)

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Total submissions: 7
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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
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
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000729804 SCV000857495 pathogenic not provided 2017-10-17 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000762933 SCV000893355 likely pathogenic Chronic obstructive pulmonary disease; Alpha-1-antitrypsin deficiency 2018-10-31 criteria provided, single submitter clinical testing
GeneReviews RCV000201848 SCV000256622 pathogenic Alpha-1-antitrypsin deficiency 2014-05-01 no assertion criteria provided literature only
Invitae RCV000201848 SCV000961591 likely pathogenic Alpha-1-antitrypsin deficiency 2018-09-11 criteria provided, single submitter clinical testing This sequence change replaces leucine with proline at codon 65 of the SERPINA1 protein (p.Leu65Pro). The leucine residue is moderately conserved and there is a moderate physicochemical difference between leucine and proline. This variant is present in population databases (rs28931569, ExAC 0.008%). This variant has been observed on the opposite chromosome (in trans) from other pathogenic variants in individuals affected with alpha 1-antitrypsin deficiency (PMID: 9635295, 3262617). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. This variant is also known as M procida and p.Leu41Pro in the literature. ClinVar contains an entry for this variant (Variation ID: 17971). Experimental studies have shown that this missense change disrupts alpha 1-antitrypsin activity (PMID: 14767073). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
OMIM RCV000019571 SCV000039868 other PI M(PROCIDA) 2016-07-15 no assertion criteria provided literature only

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