Submissions for variant NM_000527.5(LDLR):c.940+2T>C

dbSNP: rs875989912

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
LDLR-LOVD, British Heart Foundation	RCV000211690	SCV000295079	likely pathogenic	Hypercholesterolemia, familial, 1	2016-03-25	criteria provided, single submitter	literature only
Cardiovascular Research Group, Instituto Nacional de Saude Doutor Ricardo Jorge	RCV000211690	SCV000599352	pathogenic	Hypercholesterolemia, familial, 1	2016-03-01	criteria provided, single submitter	curation
Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India	RCV000211690	SCV005088709	pathogenic	Hypercholesterolemia, familial, 1		criteria provided, single submitter	clinical testing	In-silico tools (Human Splicing Finder and Splice AI) are consistent in predicting to alter the acceptor splice site which may lead to aberrant splicing leading to either the formation of a truncated protein or the transcript to undergo nonsense-mediated mRNA decay. This variant present at a consensus splice site is reported to cause intron inclusion without evidence of degradation of the mutant transcripts (Holla ØL et al., 2009). This variant is reported in the ClinVar database with pathogenic/likely pathogenic interpretation in three independent submissions (ClinVar ID: 226340). The clinical features observed in the proband and her similarly affected sibling are in concordance with hypercholesterolemia, familial, 1.
Cardiovascular Genetics Laboratory, PathWest Laboratory Medicine WA - Fiona Stanley Hospital	RCV000211690	SCV000268592	pathogenic	Hypercholesterolemia, familial, 1	2015-12-11	no assertion criteria provided	clinical testing