ClinVar Miner

Submissions for variant NM_000527.4(LDLR):c.694+2T>C (rs200238879)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
LDLR-LOVD, British Heart Foundation RCV000003936 SCV000294919 pathogenic Familial hypercholesterolemia 1 2016-03-25 criteria provided, single submitter literature only
Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies,APHP, GH Hôpitaux Universitaires Pitié-Salpêtrière / Charles-Foix RCV000003936 SCV000503226 likely pathogenic Familial hypercholesterolemia 1 2016-12-16 criteria provided, single submitter clinical testing subject mutated among 2600 FH index cases screened = 1 , family member = 1
U4M - Lille University & CHRU Lille, Université de Lille - CHRU de Lille RCV000003936 SCV000583730 pathogenic Familial hypercholesterolemia 1 2017-03-30 criteria provided, single submitter clinical testing
Fundacion Hipercolesterolemia Familiar RCV000003936 SCV000607495 pathogenic Familial hypercholesterolemia 1 2016-03-01 criteria provided, single submitter research
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001201185 SCV001372245 pathogenic Familial hypercholesterolemia 2020-06-15 criteria provided, single submitter clinical testing Variant summary: LDLR c.694+2T>C is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Four predict the variant abolishes a 5 splicing donor site. Experimental evidence supports these predictions indicating that this variant causes abnormal mRNA splicing (Gudnason_1997). The variant was absent in 244508 control chromosomes (gnomAD). c.694+2T>C has been reported in the literature in multiple individuals affected with Familial Hypercholesterolemia (e.g. Gudnason_1997, Wintjens_2016). These data indicate that the variant is very likely to be associated with disease. Four ClinVar submitters (evaluation after 2014) cite the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
OMIM RCV000003936 SCV000024101 pathogenic Familial hypercholesterolemia 1 1997-01-01 no assertion criteria provided literature only

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