Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| LDLR- |
RCV000238408 | SCV000294460 | pathogenic | Hypercholesterolemia, familial, 1 | 2016-03-25 | criteria provided, single submitter | literature only | |
| Centre de Génétique Moléculaire et Chromosomique, |
RCV000238408 | SCV000503100 | pathogenic | Hypercholesterolemia, familial, 1 | 2016-12-16 | criteria provided, single submitter | clinical testing | subjects mutated among 2600 FH index cases screened = 3 , family member = 1 with co-segregation |
| U4M - |
RCV000238408 | SCV000583629 | pathogenic | Hypercholesterolemia, familial, 1 | 2017-03-30 | criteria provided, single submitter | clinical testing | ACMG Guidelines: Pathogenic (ii) |
| Fundacion Hipercolesterolemia Familiar | RCV000238408 | SCV000607414 | pathogenic | Hypercholesterolemia, familial, 1 | 2016-03-01 | criteria provided, single submitter | research | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001532988 | SCV001748821 | pathogenic | Familial hypercholesterolemia | 2021-06-21 | criteria provided, single submitter | clinical testing | Variant summary: LDLR c.91G>T (p.Glu31X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 251034 control chromosomes (gnomAD). c.91G>T has been reported in the literature in multiple individuals affected with Familial Hypercholesterolemia. Several of these patients were of Spanish origin and in many families the variant co-segregated with high cholesterol concentrations (example: Cenarro_1996, Wintjens_2016). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four ClinVar submitters (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Ambry Genetics | RCV002446470 | SCV002682234 | pathogenic | Cardiovascular phenotype | 2018-01-28 | criteria provided, single submitter | clinical testing | The p.E31* pathogenic mutation (also known as c.91G>T), located in coding exon 2 of the LDLR gene, results from a G to T substitution at nucleotide position 91. This changes the amino acid from a glutamic acid to a stop codon within coding exon 2. This mutation (historically described as p.E10*) has been reported in multiple individuals with familial hypercholesterolemia (FH) from a variety of ancestries (Cenarro A et al. Clin. Genet., 1996 Apr;49:180-5; Reshef A et al. Hum. Genet., 1996 Nov;98:581-6; Descamps OS et al. Eur. J. Clin. Invest., 2001 Nov;31:958-65). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
| Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, |
RCV000238408 | SCV000606013 | pathogenic | Hypercholesterolemia, familial, 1 | no assertion criteria provided | research |