Submissions for variant NM_000527.5(LDLR):c.925_931del (p.Pro309fs)

dbSNP: rs387906304

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
LDLR-LOVD, British Heart Foundation	RCV000003927	SCV000295060	pathogenic	Hypercholesterolemia, familial, 1	2016-03-25	criteria provided, single submitter	literature only
Cardiovascular Research Group, Instituto Nacional de Saude Doutor Ricardo Jorge	RCV000003927	SCV000599351	pathogenic	Hypercholesterolemia, familial, 1	2016-03-01	criteria provided, single submitter	curation
Labcorp Genetics (formerly Invitae), Labcorp	RCV000810136	SCV000950326	pathogenic	Familial hypercholesterolemia	2019-01-29	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in LDLR are known to be pathogenic (PMID: 20809525). This sequence change creates a premature translational stop signal (p.Pro309Lysfs*59) in the LDLR gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed to segregate with familial hypercholesterolemia in multiple families (PMID: 1634609, 9409302). This variant is also known as a founder mutation FH-North Karelia in the literature. ClinVar contains an entry for this variant (Variation ID: 3729).
Mayo Clinic Laboratories, Mayo Clinic	RCV004791195	SCV005413307	pathogenic	not provided	2024-05-31	criteria provided, single submitter	clinical testing	PS4, PVS1
OMIM	RCV000003927	SCV000024092	pathogenic	Hypercholesterolemia, familial, 1	1997-11-01	no assertion criteria provided	literature only
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum	RCV000003927	SCV000606271	pathogenic	Hypercholesterolemia, familial, 1		no assertion criteria provided	research