ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.1060+10G>A

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
LDLR-LOVD, British Heart Foundation RCV000238168 SCV000295175 likely benign Familial hypercholesterolemia 1 2016-03-25 criteria provided, single submitter literature only
Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies,APHP, GH Hôpitaux Universitaires Pitié-Salpêtrière / Charles-Foix RCV000238168 SCV000503290 likely pathogenic Familial hypercholesterolemia 1 2016-12-16 criteria provided, single submitter clinical testing subjects mutated among 2600 FH index cases screened = 6 , family member = 1
Laboratory of Genetics and Molecular Cardiology, University of São Paulo RCV000238168 SCV000588547 uncertain significance Familial hypercholesterolemia 1 2016-03-01 criteria provided, single submitter research
Fundacion Hipercolesterolemia Familiar RCV000238168 SCV000607553 uncertain significance Familial hypercholesterolemia 1 2016-03-01 criteria provided, single submitter research
Robarts Research Institute,Western University RCV000238168 SCV000782906 uncertain significance Familial hypercholesterolemia 1 2018-01-02 criteria provided, single submitter clinical testing
Invitae RCV001242346 SCV001415427 uncertain significance Familial hypercholesterolemia 2019-04-24 criteria provided, single submitter clinical testing This sequence change falls in intron 7 of the LDLR gene. It does not directly change the encoded amino acid sequence of the LDLR protein. This variant is present in population databases (rs12710260, ExAC 0.006%). This variant has been observed in several individuals affected with hypercholesterolemia (PMID: 12436241, 15823288,23375686). ClinVar contains an entry for this variant (Variation ID: 251625). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Laboratory of molecular diagnosis of dyslipidemias, Università egli studi di Napoli Federico II RCV000238168 SCV001653618 pathogenic Familial hypercholesterolemia 1 2021-05-24 criteria provided, single submitter clinical testing
GeneDx RCV001576239 SCV001803385 uncertain significance not provided 2020-09-03 criteria provided, single submitter clinical testing Identified in both heterozygous and homozygous states in several unrelated individuals with a clinical diagnosis of FH (Amsellem et al., 2002; Damgaard et al., 2005; Bertolini et al., 2013; Pirillo et al., 2017); Not observed at a significant frequency in large population cohorts (Lek et al., 2016); Reported in ClinVar but additional evidence is not available (ClinVar Variant ID#251625; Landrum et al., 2016); In silico analysis, which includes splice predictors and evolutionary conservation, suggests this variant may impact gene splicing; in the absence of RNA/functional studies, the actual effect of this sequence change is unknown; This variant is associated with the following publications: (PMID: 28965616, 23375686, 15823288, 12436241, 26332594)
Broad Institute Rare Disease Group, Broad Institute RCV000238168 SCV001422917 uncertain significance Familial hypercholesterolemia 1 2020-01-22 no assertion criteria provided curation The c.1060+10G>A variant in LDLR has been reported in 6 individuals (including 3 French and 2 Italian individuals) with Familial Hypercholesterolemia, segregated with disease in 2 affected relatives from 1 family (PMID: 12436241, 23375686, 28965616), and has been identified in 0.01088% (2/18376) of East Asian chromosomes and 0.003267% (1/30608) of South Asian chromosomes by the Genome Aggregation Database (gnomAD,; dbSNP rs12710260). This variant has also been reported as a VUS, a likely benign variant, and a likely pathogenic variant in ClinVar (Variation ID: 251625). Please note that for diseases with clinical variability, or reduced penetrance, pathogenic variants may be present at a low frequency in the general population. Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the c.1060+10G>A variant is uncertain. ACMG/AMP Criteria applied: PS4_Supporting (Richards 2015).

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