Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
LDLR- |
RCV000003936 | SCV000294919 | pathogenic | Familial hypercholesterolemia 1 | 2016-03-25 | criteria provided, single submitter | literature only | |
Centre de Génétique Moléculaire et Chromosomique, |
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 - |
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 | |
Integrated Genetics/Laboratory Corporation of America | 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 |