Submissions for variant NM_000237.3(LPL):c.213C>G (p.His71Gln)

dbSNP: rs11542065

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004767424	SCV000696008	likely benign	not specified	2024-08-05	criteria provided, single submitter	clinical testing	Variant summary: LPL c.213C>G (p.His71Gln) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00084 in 251790 control chromosomes, predominantly at a frequency of 0.013 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 4 fold of the estimated maximal expected allele frequency for a pathogenic variant in LPL causing Familial Lipoprotein Lipase Deficiency phenotype (0.0034). one study identified the variant in 9 of 208 patients with familial hyperlipidemia but did not detect the variant in 171 control individuals, revealing an enrichment of the variant in patients (odds ratio of 16.33 [95% CI = 0.94 - 282.7], Minicocci_2015)(As calculated using the online OR calculator tool, MEDCALC using the case controls data published in Minicocci_Athero_2015). As the 95% CI overlaps 1 there is little confidence in the strength of this assertion and additional large studies would be needed to validate this finding. This variant was also reported in two more individuals from a cohort of hypertriglyceridemia, without primary information (Deshotels_2022). These report(s) do not provide unequivocal conclusions about association of the variant with Familial Lipoprotein Lipase Deficiency. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 36325899, 26342331). ClinVar contains an entry for this variant (Variation ID: 495743). Based on the evidence outlined above, the variant was classified as likely benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000588713	SCV001116083	benign	not provided	2024-01-29	criteria provided, single submitter	clinical testing
GeneDx	RCV000588713	SCV001834626	benign	not provided	2021-03-22	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 33303402, 22129523)
Natera, Inc.	RCV001272627	SCV001454750	likely benign	Hyperlipoproteinemia, type I	2020-01-10	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003980065	SCV004792845	benign	LPL-related disorder	2019-12-06	no assertion criteria provided	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).