ClinVar Miner

Submissions for variant NM_000237.3(LPL):c.1279G>A (p.Ala427Thr) (rs5934)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000328685 SCV000472759 likely benign Hyperlipoproteinemia, type I 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000586674 SCV000696007 likely benign not provided 2017-06-08 criteria provided, single submitter clinical testing Variant summary: The LPL c.1279G>A (p.Ala427Thr) variant involves the alteration of a non-conserved nucleotide, resulting in a missense substitution in the PLAT/LH2 domain (InterPro). 3/4 in silico tools predict a benign outcome for this variant (SNPsandGO not captured due to low reliability index). This variant was found in the large control database ExAC and control cohorts reported in the literature in 396 of 122640 control chromosomes (3 homozygotes) of all ethnicities, but was predominantly observed in the African subpopulation at a frequency of 0.028657 (297/10364; 2 homozygotes). This frequency is about 9 times the estimated maximal expected allele frequency of a pathogenic LPL variant (0.0033541), suggesting this is likely a benign polymorphism found primarily in the populations of African origin. The variant has been identified in several patients diagnosed with hypertriglyceridemia without strong evidence for causality (such as cosegregation with disease), including one study where the variant was significantly enriched in patients compared to controls (8/208 patients vs. 0/171 controls; p=0.009 as reported by the authors; Minicocci_2015). However, sample size was small and more studies are needed to confirm this. A functional study showed in a patient carrying the variant and LMF1 variant of unknown significance (p.Gly36Asp), had normal levels of LPL enzyme activity (Surendran_2012), suggesting the variant does not impair LPL enzyme activity. In addition, one clinical diagnostic laboratory has classified this variant as likely benign with no supporting evidence provided. Taken together, this variant is classified as Likely Benign.
Invitae RCV000586674 SCV001093266 benign not provided 2020-12-01 criteria provided, single submitter clinical testing

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