Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001837943 | SCV001202004 | benign | Hypercholesterolemia, autosomal dominant, type B; Familial hypobetalipoproteinemia 1 | 2023-11-14 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV001837943 | SCV002781101 | uncertain significance | Hypercholesterolemia, autosomal dominant, type B; Familial hypobetalipoproteinemia 1 | 2021-12-20 | criteria provided, single submitter | clinical testing | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV003478083 | SCV004220726 | uncertain significance | not provided | 2023-08-29 | criteria provided, single submitter | clinical testing | In the published literature, this variant has been reported in individuals and families affected by hypercholesterolemia (PMIDs: 17964958 (2007), 18325181 (2008), 23775634 (2013), 34428338 (2021)) as well as cardiac disease (PMIDs: 34573395 (2021), 35979295 (2022)). The frequency of this variant in the general population, 0.00015 (3/19940 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded conflicting predictions that this variant is deleterious or benign. Based on the available information, we are unable to determine the clinical significance of this variant. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV003488644 | SCV004241703 | likely benign | not specified | 2024-08-12 | criteria provided, single submitter | clinical testing | Variant summary: APOB c.10700C>T (p.Thr3567Met) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 7.2e-05 in 250866 control chromosomes. The observed variant frequency is higher than the estimated maximal expected allele frequency for a pathogenic variant in APOB causing Familial Hypercholesterolemia phenotype (6.3e-05). c.10700C>T has been reported in the literature in many individuals affected with Familial Hypercholesterolemia (e.g., Yang_2007, Liyanage_2008, Kusters_2013, Elfatih_2021, Yang_2022, Ibrahim_2023), and the variant was said to segregate with disease in at least one family although no data was provided (e.g., Yang_2007). The variant was also reported in at least one individual affected with Tetralogy of Fallot (Pan_2022) as well as one control individual (Johansen_2010). These report(s) do not provide unequivocal conclusions about association of the variant with Familial Hypercholesterolemia. Additionally, a co-occurrence with another pathogenic variant was reported in a mother and son affected with Familial Hypercholesterolemia (LDLR c.1448G>A, p.W483X; Yang_2022), providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 34428338, 20657596, 23833242, 18325181, 36071769, 17964958, 35979295, 37675602). ClinVar contains an entry for this variant (Variation ID: 440520). Based on the evidence outlined above, the variant was classified as likely benign. |
Ambry Genetics | RCV004023444 | SCV004906204 | uncertain significance | Cardiovascular phenotype | 2023-12-05 | criteria provided, single submitter | clinical testing | Unlikely to be causative of APOB-related hypobetalipoproteinemia (AR) Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, |
RCV000508852 | SCV000605961 | pathogenic | Hypercholesterolemia, familial, 1 | no assertion criteria provided | research | ||
Amrita Institute of Medical Sciences and Research Centre, |
RCV004023444 | SCV005205801 | uncertain significance | Cardiovascular phenotype | 2023-05-02 | no assertion criteria provided | clinical testing | Previously reported by SCV001202004 |