Total submissions: 9
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Soonchunhyang University Bucheon Hospital, |
RCV000237176 | SCV000267384 | uncertain significance | Familial hypercholesterolemia 1 | 2016-03-18 | criteria provided, single submitter | reference population | |
LDLR- |
RCV000237176 | SCV000294641 | likely pathogenic | Familial hypercholesterolemia 1 | 2016-03-25 | criteria provided, single submitter | literature only | |
Centre de Génétique Moléculaire et Chromosomique, |
RCV000237176 | SCV000503144 | likely benign | Familial hypercholesterolemia 1 | 2016-12-16 | criteria provided, single submitter | clinical testing | subject mutated among 2600 FH index cases screened = 1 /previously described in association with FH / Software predictions: Conflicting |
Cardiovascular Research Group, |
RCV000237176 | SCV000599327 | pathogenic | Familial hypercholesterolemia 1 | 2016-03-01 | criteria provided, single submitter | curation | |
Color Health, |
RCV000771221 | SCV000903315 | uncertain significance | Familial hypercholesterolemia | 2019-12-19 | criteria provided, single submitter | clinical testing | |
Illumina Clinical Services Laboratory, |
RCV000237176 | SCV000915812 | likely pathogenic | Familial hypercholesterolemia 1 | 2017-05-01 | criteria provided, single submitter | clinical testing | The LDLR c.344G>A (p.Arg115His) missense variant has been reported in five studies and is found in a total of eight individuals with hypercholesterolemia, including one individual who carried the variant in a compound heterozygous state with a stop-gained variant and seven individuals who carried the variant in a heterozygous state (Khoo et al. 2000; Yu et al. 2002; Kim et al. 2004; Chiou et al. 2011; Mabuchi et al. 2011). Control data are unavailable for this variant, which is reported at a frequency of 0.00234 in the East Asian population of the Genome Aggregation Database. Based on the evidence, the p.Arg115His variant is classified as likely pathogenic for familial hypercholesterolemia. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |
Invitae | RCV000771221 | SCV001225051 | uncertain significance | Familial hypercholesterolemia | 2019-11-01 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with histidine at codon 115 of the LDLR protein (p.Arg115His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs201102461, ExAC 0.2%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has been observed in individuals affected with familial hypercholesterolemia (PMID: 9399845, 15359125, 29399563, 28502495, 18718593, 28932795, 11005141, 12417285). This variant is also known as R94H in the literature. ClinVar contains an entry for this variant (Variation ID: 225402). This variant has been reported to have conflicting or insufficient data to determine the effect on LDLR protein function (PMID: 12837857, 27821657). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, |
RCV000237176 | SCV000606093 | pathogenic | Familial hypercholesterolemia 1 | no assertion criteria provided | research | ||
Natera, |
RCV000771221 | SCV001456140 | uncertain significance | Familial hypercholesterolemia | 2020-09-16 | no assertion criteria provided | clinical testing |