Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| LDLR- |
RCV000237770 | SCV000295223 | likely pathogenic | Hypercholesterolemia, familial, 1 | 2016-03-25 | criteria provided, single submitter | literature only | |
| Labcorp Genetics |
RCV000824031 | SCV000964906 | pathogenic | Familial hypercholesterolemia | 2018-07-07 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. 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 to segregate with familial hypercholesterolemia in several families, including a family member who was homozygous for this variant (PMID: 23375686). This variant is also known as p.N349T in the literature. ClinVar contains an entry for this variant (Variation ID: 251668). This variant is not present in population databases (ExAC no frequency). This sequence change replaces asparagine with threonine at codon 370 of the LDLR protein (p.Asn370Thr). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and threonine. |
| Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, |
RCV000237770 | SCV001433521 | likely pathogenic | Hypercholesterolemia, familial, 1 | 2020-01-31 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV004992119 | SCV005612300 | likely pathogenic | Cardiovascular phenotype | 2024-11-29 | criteria provided, single submitter | clinical testing | The p.N370T variant (also known as c.1109A>C), located in coding exon 8 of the LDLR gene, results from an A to C substitution at nucleotide position 1109. The asparagine at codon 370 is replaced by threonine, an amino acid with similar properties. This variant was identified in one or more individuals with features consistent with familial hypercholesterolemia, including a homozygous case, and segregated with disease in at least one family (Bertolini S et al. Arterioscler Thromb Vasc Biol, 2000 Sep;20:E41-52; Bertolini S et al. Atherosclerosis, 2013 Apr;227:342-8). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic. |