Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
LDLR- |
RCV000237817 | SCV000295739 | likely pathogenic | Hypercholesterolemia, familial, 1 | 2016-03-25 | criteria provided, single submitter | literature only | |
Invitae | RCV001857832 | SCV002185875 | uncertain significance | Familial hypercholesterolemia | 2021-04-06 | criteria provided, single submitter | clinical testing | 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. 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been observed in individual(s) with Familial hypercholesterolemia (PMID: 15199436). ClinVar contains an entry for this variant (Variation ID: 252103). This variant is also described as I607T in the literature. This variant is not present in population databases (ExAC no frequency). This sequence change replaces isoleucine with threonine at codon 628 of the LDLR protein (p.Ile628Thr). The isoleucine residue is highly conserved and there is a moderate physicochemical difference between isoleucine and threonine. |
Ambry Genetics | RCV002411103 | SCV002721184 | uncertain significance | Cardiovascular phenotype | 2020-08-07 | criteria provided, single submitter | clinical testing | The p.I628T variant (also known as c.1883T>C), located in coding exon 13 of the LDLR gene, results from a T to C substitution at nucleotide position 1883. The isoleucine at codon 628 is replaced by threonine, an amino acid with similar properties. This variant (described as legacy p.I607T) was reported in a Norwegian hypercholesterolemia genetic testing cohort; however, clinical details were limited (Leren TP et al. Semin Vasc Med, 2004 Feb;4:75-85). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |