Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
LDLR- |
RCV000238120 | SCV000295906 | likely benign | Hypercholesterolemia, familial, 1 | 2016-03-25 | criteria provided, single submitter | literature only | |
Color Diagnostics, |
RCV001804978 | SCV002053091 | uncertain significance | Familial hypercholesterolemia | 2021-04-13 | criteria provided, single submitter | clinical testing | This missense variant (also known as p.Thr703Ile in the mature protein) replaces threonine with isoleucine at codon 724 of the LDLR protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with familial hypercholesterolemia in the literature. This variant has been identified in 2/251224 chromosomes in the general population by the Genome Aggregation Database (gnomAD). 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. |
Labcorp Genetics |
RCV001804978 | SCV002175403 | uncertain significance | Familial hypercholesterolemia | 2021-12-18 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 724 of the LDLR protein (p.Thr724Ile). This variant is present in population databases (no rsID available, gnomAD 0.002%). This missense change has been observed in individual(s) with familial hypercholesterolemia (PMID: 23375686). ClinVar contains an entry for this variant (Variation ID: 252246). 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 tolerated. 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. |