ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.661delinsATCAC (p.Asp221fs)

dbSNP: rs2077280444
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001246803 SCV001420188 pathogenic Familial hypercholesterolemia 2019-07-17 criteria provided, single submitter clinical testing This variant is not present in population databases (ExAC no frequency). For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in LDLR are known to be pathogenic (PMID: 20809525, 28645073). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with LDLR-related conditions. This sequence change creates a premature translational stop signal (p.Asp221Ilefs*8) in the LDLR gene. It is expected to result in an absent or disrupted protein product.
Ambry Genetics RCV002366084 SCV002663161 pathogenic Cardiovascular phenotype 2020-12-24 criteria provided, single submitter clinical testing The c.661delGinsATCAC pathogenic mutation, located in coding exon 4 of the LDLR gene, results from the deletion of one nucleotide and insertion of 5 nucleotides causing a translational frameshift with a predicted alternate stop codon (p.D221Ifs*8). 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.

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