Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
LDLR- |
RCV000238432 | SCV000295815 | likely pathogenic | Hypercholesterolemia, familial, 1 | 2016-03-25 | criteria provided, single submitter | literature only | |
U4M - |
RCV000238432 | SCV000583919 | pathogenic | Hypercholesterolemia, familial, 1 | 2017-03-30 | criteria provided, single submitter | clinical testing | |
Institute of Human Genetics, |
RCV000238432 | SCV001428688 | likely pathogenic | Hypercholesterolemia, familial, 1 | 2019-11-21 | criteria provided, single submitter | clinical testing | This variant was identified as homozygous |
Prevention |
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. |