ClinVar Miner

Submissions for variant NM_000295.5(SERPINA1):c.646+1G>T

gnomAD frequency: 0.00001  dbSNP: rs751235320
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169461 SCV000220891 likely pathogenic Alpha-1-antitrypsin deficiency 2014-11-14 criteria provided, single submitter literature only
Eurofins Ntd Llc (ga) RCV000593270 SCV000706472 likely pathogenic not provided 2017-02-21 criteria provided, single submitter clinical testing
Invitae RCV000169461 SCV002245454 pathogenic Alpha-1-antitrypsin deficiency 2023-08-08 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. Studies have shown that disruption of this splice site alters SERPINA1 gene expression (PMID: 8364536). ClinVar contains an entry for this variant (Variation ID: 189064). This variant has not been reported in the literature in individuals affected with SERPINA1-related conditions. This variant is present in population databases (rs751235320, gnomAD 0.0009%). This sequence change affects a donor splice site in intron 2 of the SERPINA1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in SERPINA1 are known to be pathogenic (PMID: 25425243).
Baylor Genetics RCV000169461 SCV004203125 likely pathogenic Alpha-1-antitrypsin deficiency 2023-07-19 criteria provided, single submitter clinical testing
OMIM RCV000019606 SCV000039904 other PI NULL(WEST) 2016-07-15 no assertion criteria provided literature only
Department of Laboratory Medicine and Genetics, Trillium Health Partners Credit Valley Hospital RCV000169461 SCV000608321 pathogenic Alpha-1-antitrypsin deficiency 2014-12-08 no assertion criteria provided curation

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