Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
LDLR- |
RCV000211699 | SCV000294857 | pathogenic | Hypercholesterolemia, familial, 1 | 2016-03-25 | criteria provided, single submitter | literature only | |
Labcorp Genetics |
RCV000824495 | SCV000965394 | pathogenic | Familial hypercholesterolemia | 2021-02-10 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant has been observed in several individuals affected with familial hypercholesterolemia (PMID: 9678702, 11139254, 22883975, 11462246, 15556094). This variant is also known as P199fsX243, 657delC. ClinVar contains an entry for this variant (Variation ID: 226330). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Asp221Thrfs*44) 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). |
Brunham Lab, |
RCV000211699 | SCV001432618 | pathogenic | Hypercholesterolemia, familial, 1 | 2019-05-11 | criteria provided, single submitter | research | |
Ambry Genetics | RCV002363057 | SCV002664460 | pathogenic | Cardiovascular phenotype | 2023-12-13 | criteria provided, single submitter | clinical testing | The c.660delC (p.D221Tfs*44) alteration, located in exon 4 (coding exon 4) of the LDLR gene, consists of a deletion of one nucleotide at position 660, causing a translational frameshift with a predicted alternate stop codon after 44 amino acids. Frameshift alterations are typically deleterious in nature (Richards, 2015). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This mutation (also described as c.657delC) has been reported in numerous familial hypercholesterolemia (FH) cohorts from a variety of ethnic backgrounds (Lee, 1998; Bochmann, 2001; Laurie, 2004; Bamimore, 2015; Hu, 2016). Based on the available evidence, this alteration is classified as pathogenic. |
Gene |
RCV003235135 | SCV003933319 | pathogenic | not provided | 2022-12-14 | criteria provided, single submitter | clinical testing | Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 34037665, 9678702) |
Cardiovascular Genetics Laboratory, |
RCV000211699 | SCV000268575 | pathogenic | Hypercholesterolemia, familial, 1 | 2014-05-05 | no assertion criteria provided | clinical testing | |
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, |
RCV000211699 | SCV000606183 | pathogenic | Hypercholesterolemia, familial, 1 | no assertion criteria provided | research | ||
Natera, |
RCV000824495 | SCV002086377 | pathogenic | Familial hypercholesterolemia | 2020-12-07 | no assertion criteria provided | clinical testing |