ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.230del (p.Gly77fs)

dbSNP: rs879254440
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
LDLR-LOVD, British Heart Foundation RCV000237844 SCV000294539 pathogenic Hypercholesterolemia, familial, 1 2016-03-25 criteria provided, single submitter literature only
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000589330 SCV000697225 likely pathogenic Familial hypercholesterolemia 2017-05-19 criteria provided, single submitter clinical testing Variant summary: The LDLR c.230delG (p.Gly77Alafs) variant results in a premature termination codon, predicted to cause a truncated or absent LDLR protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. c.285C>A, p.Cys95X; c.337G>T, p.Glu113X; c.338_353delAGTTTCGCTGCCACGA, p.Glu113fs). One in silico tool predicts a damaging outcome for this variant. The variant of interest has not been found in a large, broad control population, ExAC in 121412 control chromosomes. This variant was identified in one Japanese cohort in a FH patient (Yu_Atherosclerosis_2002). In addition, one reputable database classified this variant as pathogenic. Taken together, this variant is classified as likely pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV000589330 SCV003250500 pathogenic Familial hypercholesterolemia 2023-08-07 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 251082). This premature translational stop signal has been observed in individual(s) with familial hypercholesterolemia (PMID: 12417285, 32331935). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gly77Alafs*129) in the LDLR gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in LDLR are known to be pathogenic (PMID: 20809525, 28645073).
GeneDx RCV004701334 SCV005201879 pathogenic not provided 2023-08-18 criteria provided, single submitter clinical testing Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 32331935, 12417285)
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum RCV000237844 SCV000606044 pathogenic Hypercholesterolemia, familial, 1 no assertion criteria provided research

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