ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.1335C>G (p.Asp445Glu)

gnomAD frequency: 0.00003  dbSNP: rs749780672
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000819259 SCV000959909 uncertain significance Familial hypercholesterolemia 2021-09-01 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with glutamic acid at codon 445 of the LDLR protein (p.Asp445Glu). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and glutamic acid. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individual(s) with familial hypercholesterolemia (PMID: 7573037, 15199436). This variant is also known as p.Asp242Glu and FH-Fin-8. ClinVar contains an entry for this variant (Variation ID: 661768). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. Experimental studies have shown that this missense change does not substantially affect LDLR function (PMID: 31587492). 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.
Fulgent Genetics, Fulgent Genetics RCV002487822 SCV002778398 uncertain significance Hypercholesterolemia, familial, 1 2021-07-30 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System RCV002487822 SCV006057244 uncertain significance Hypercholesterolemia, familial, 1 2020-05-26 criteria provided, single submitter research
Natera, Inc. RCV000819259 SCV002086417 uncertain significance Familial hypercholesterolemia 2020-08-24 no assertion criteria provided clinical testing

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