ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.169G>A (p.Asp57Asn)

dbSNP: rs879254420
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Familial Hypercholesterolemia Variant Curation Expert Panel RCV000238214 SCV002817135 uncertain significance Hypercholesterolemia, familial, 1 2022-08-29 reviewed by expert panel curation The NM_000527.5(LDLR):c.169G>A (p.Asp57Asn) variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying evidence codes PM2, PP3, and PP4 as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (https://doi.org/10.1016/j.gim.2021.09.012). The supporting evidence is as follows: PM2: This variant is absent from gnomAD (gnomAD v2.1.1.). So PM2 is met. PP3: REVEL= 0.791. It is above 0.75, so PP3 is met. PP4: Variant meets PM2 and is identified in 1 case fulfilling WHO criteria published in PMID: 20145306 (Chmara et al., 2010). So PP4 is met.
LDLR-LOVD, British Heart Foundation RCV003765484 SCV000294491 uncertain significance Familial hypercholesterolemia 2016-03-25 criteria provided, single submitter literature only Reevaluation of the ACMG criteria for this entry: PM2, PP3 and PS4 can be scored. Therefore the classification is for Uncertain significance.
Illumina Laboratory Services, Illumina RCV000238214 SCV001281757 uncertain significance Hypercholesterolemia, familial, 1 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
GeneDx RCV003329270 SCV004036308 uncertain significance not provided 2023-03-22 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 25525159, 22881376, 35910211, 20145306)
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum RCV000238214 SCV000606030 pathogenic Hypercholesterolemia, familial, 1 flagged submission research

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