Submissions for variant NM_000527.5(LDLR):c.966del (p.Asn322fs)

dbSNP: rs2077361078

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001042537	SCV001206220	pathogenic	Familial hypercholesterolemia	2019-04-19	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, 28645073). This variant has not been reported in the literature in individuals with LDLR-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Asn322Lysfs*48) in the LDLR gene. It is expected to result in an absent or disrupted protein product.
Ambry Genetics	RCV002379508	SCV002693902	pathogenic	Cardiovascular phenotype	2019-06-26	criteria provided, single submitter	clinical testing	The c.966delC pathogenic mutation, located in coding exon 7 of the LDLR gene, results from a deletion of one nucleotide at nucleotide position 966, causing a translational frameshift with a predicted alternate stop codon (p.N322Kfs*48). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.