ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.1061A>C (p.Asp354Ala)

dbSNP: rs755449669
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
LDLR-LOVD, British Heart Foundation RCV000238540 SCV000295190 likely pathogenic Hypercholesterolemia, familial, 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 RCV000238540 SCV000503292 likely pathogenic Hypercholesterolemia, familial, 1 2016-12-16 criteria provided, single submitter clinical testing subject mutated among 2600 FH index cases screened = 1 /FH-Austria / Software predictions: Damaging
Molecular Genetics Laboratory, Centre for Cardiovascular Surgery and Transplantation RCV000238540 SCV000540787 likely pathogenic Hypercholesterolemia, familial, 1 2016-11-05 criteria provided, single submitter clinical testing
Ambry Genetics RCV004639192 SCV005135987 likely pathogenic Cardiovascular phenotype 2024-03-26 criteria provided, single submitter clinical testing The p.D354A variant (also known as c.1061A>C) is located in coding exon 8 of the LDLR gene. The aspartic acid at codon 354 is replaced by alanine, an amino acid with dissimilar properties. This change occurs in the first base pair of coding exon 8. This alteration has been reported in association with familial hypercholesterolemia (FH) (Marduel M et al. Hum Mutat, 2010 Nov;31:E1811-24; Tichý L et al. Atherosclerosis, 2012 Aug;223:401-8). Another variant at the same codon, p.D354G (c.1061A>G), has also been detected in subjects with FH (Hobbs HH et al. Hum Mutat, 1992;1:445-66). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the majority of available evidence to date, this variant is likely to be pathogenic.

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