ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.671A>G (p.Asp224Gly)

dbSNP: rs879254630
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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 RCV000238189 SCV000294884 likely pathogenic Hypercholesterolemia, familial, 1 2016-03-25 criteria provided, single submitter literature only
Labcorp Genetics (formerly Invitae), Labcorp RCV001208294 SCV001379674 pathogenic Familial hypercholesterolemia 2022-10-20 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Asp224 amino acid residue in LDLR. Other variant(s) that disrupt this residue have been observed in individuals with LDLR-related conditions (PMID: 7649546, 16627557), which suggests that this may be a clinically significant amino acid residue. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt LDLR protein function. ClinVar contains an entry for this variant (Variation ID: 251374). This variant is also known as p.D203G. This missense change has been observed in individuals with hypercholesterolemia (PMID: 1301956, 17539906, 23375686; Invitae). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 224 of the LDLR protein (p.Asp224Gly).
Laboratory of molecular diagnosis of dyslipidemias, Università egli studi di Napoli Federico II RCV000238189 SCV001653601 likely pathogenic Hypercholesterolemia, familial, 1 2021-05-24 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000238189 SCV002812285 likely pathogenic Hypercholesterolemia, familial, 1 2022-02-17 criteria provided, single submitter clinical testing

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