Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
LDLR- |
RCV000238040 | SCV000295334 | likely pathogenic | Hypercholesterolemia, familial, 1 | 2016-03-25 | criteria provided, single submitter | literature only | |
Centre de Génétique Moléculaire et Chromosomique, |
RCV000238040 | SCV000503326 | likely pathogenic | Hypercholesterolemia, familial, 1 | 2016-12-16 | criteria provided, single submitter | clinical testing | subjects mutated among 2600 FH index cases screened = 15 , family members = 6 with co-segregation / variant systematically associated with c.798T>A, p.Asp266Glu / Software predictions: Conflicting |
Cardiovascular Research Group, |
RCV000238040 | SCV000599370 | pathogenic | Hypercholesterolemia, familial, 1 | 2016-03-01 | criteria provided, single submitter | curation | |
Labcorp Genetics |
RCV001384956 | SCV001584659 | pathogenic | Familial hypercholesterolemia | 2020-03-04 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine with threonine at codon 423 of the LDLR protein (p.Ile423Thr). The isoleucine residue is highly conserved and there is a moderate physicochemical difference between isoleucine and threonine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with familial hypercholesterolemia (PMID: 7635461, 24722143, 11005141, 10884919, Invitae). It has also been observed to segregate with disease in related individuals. This variant is also known as p.I402T in the literature. ClinVar contains an entry for this variant (Variation ID: 251760, 430765). This variant has been reported to affect LDLR protein function (PMID: 10884919). For these reasons, this variant has been classified as Pathogenic. |
Ambry Genetics | RCV002446477 | SCV002682617 | pathogenic | Cardiovascular phenotype | 2018-03-06 | criteria provided, single submitter | clinical testing | The p.I423T pathogenic mutation (also known as c.1268T>C), located in coding exon 9 of the LDLR gene, results from a T to C substitution at nucleotide position 1268. The isoleucine at codon 423 is replaced by threonine, an amino acid with similar properties. This alteration (historically described as p.I402T) has been reported in individuals with familial hypercholesterolemia and segregated with the disease in two apparently unrelated families (Ekström U et al. MP, Mol. Pathol., 2000 Feb;53:31-6; Khoo KL et al. Clin. Genet., 2000 Aug;58:98-105; Amsellem S et al. Hum. Genet., 2002 Dec;111:501-10; Wu WF et al. PLoS ONE, 2014 Apr;9:e94697). In addition, functional studies have suggested that this alteration would cause reduced protein activity in LDL binding and degradation (Ekström U et al. MP, Mol. Pathol., 2000 Feb;53:31-6). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. |
Juno Genomics, |
RCV000238040 | SCV005418438 | pathogenic | Hypercholesterolemia, familial, 1 | criteria provided, single submitter | clinical testing | PM2_Supporting+PS3+PS4_Moderate+PP4+PM3 | |
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, |
RCV000238040 | SCV000606378 | pathogenic | Hypercholesterolemia, familial, 1 | no assertion criteria provided | research |