Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
LDLR- |
RCV000237888 | SCV000295877 | pathogenic | Hypercholesterolemia, familial, 1 | 2016-03-25 | criteria provided, single submitter | literature only | |
Invitae | RCV001051686 | SCV001215854 | pathogenic | Familial hypercholesterolemia | 2023-04-22 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 252223). For these reasons, this variant has been classified as Pathogenic. This variant is also known as 2108ins7, 2114ins7, and FsR685. This premature translational stop signal has been observed in individuals with familial hypercholesterolemia (PMID: 11005141, 11313767, 30592178). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg706Alafs*13) in the LDLR gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in LDLR are known to be pathogenic (PMID: 20809525, 28645073). |
Ambry Genetics | RCV003372666 | SCV004085715 | pathogenic | Inborn genetic diseases | 2023-07-26 | criteria provided, single submitter | clinical testing | The c.2108_2114dupTGCTGGC (p.R706Afs*13) alteration, located in exon 14 (coding exon 14) of the LDLR gene, consists of a duplication of TGCTGGC at position 2108, causing a translational frameshift with a predicted alternate stop codon after 13 amino acids. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This alteration has been reported in multiple individuals with either a clinical diagnosis of familial hypercholesterolemia (FH) or a probable diagnosis of FH (Khoo, 2000; Pek, 2018). Based on the available evidence, this alteration is classified as pathogenic. |