ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.2001T>G (p.Cys667Trp)

dbSNP: rs879255109
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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 RCV000238432 SCV000295815 likely pathogenic Hypercholesterolemia, familial, 1 2016-03-25 criteria provided, single submitter literature only
U4M - Lille University & CHRU Lille, Université de Lille - CHRU de Lille RCV000238432 SCV000583919 pathogenic Hypercholesterolemia, familial, 1 2017-03-30 criteria provided, single submitter clinical testing
Institute of Human Genetics, University of Leipzig Medical Center RCV000238432 SCV001428688 likely pathogenic Hypercholesterolemia, familial, 1 2019-11-21 criteria provided, single submitter clinical testing This variant was identified as homozygous
PreventionGenetics, part of Exact Sciences RCV003417848 SCV004107569 pathogenic LDLR-related condition 2023-06-16 criteria provided, single submitter clinical testing The LDLR c.2001T>G variant is predicted to result in the amino acid substitution p.Cys667Trp. This variant, also known as Cys646Trp using legacy nomenclature, was reported in an individual with hypercholesterolemia (Patient C4 in Nissen et al 1998. PubMed ID: 9727746). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Of note, several other missense variant impacting the same amino acid (p.Cys667Ser, p.Cys667Arg, p.Cys667Tyr and p.Cys667Phe) have been reported in patients with hypercholesterolemia (Zakharova et al. 2005. PubMed ID: 15701167; Vergopoulos et al. 1997. PubMed ID: 9412789; Leitersdorf. 1990. PubMed ID: 2318961; Heath et al. 2001. PubMed ID: 11313767). Based on this evidence, we interpret the c.2001T>G (p.Cys667Trp) variant as pathogenic.

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