Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
LDLR- |
RCV000237434 | SCV000294960 | likely pathogenic | Hypercholesterolemia, familial, 1 | 2016-03-25 | criteria provided, single submitter | literature only | |
All of Us Research Program, |
RCV000237434 | SCV004837567 | uncertain significance | Hypercholesterolemia, familial, 1 | 2023-10-06 | criteria provided, single submitter | clinical testing | This missense variant replaces cysteine with glycine at codon 255 of the LDLR protein. This variant is also known as p.Cys234Gly in the mature protein. This variant alters a conserved cysteine residue that is critical for proper protein folding and function (PMID: 2088165, 6091915, 15952897). Computational prediction suggests that this variant may have a deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in individuals affected with familial hypercholesterolemia (PMID: 15823276, 16250003, 23833242, 32770674). In several of these instances, this variant has been reported to occur in cis or in unknown phase with p.Gln254His (PMID: 15823276, 23833242, 32770674). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |