ClinVar Miner

Submissions for variant NM_000384.3(APOB):c.10520G>C (p.Arg3507Pro) (rs201156840)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000230104 SCV000284753 likely benign Familial hypercholesterolemia 2; Hypobetalipoproteinemia, familial, 1 2020-12-01 criteria provided, single submitter clinical testing
Color Health, Inc RCV000776473 SCV000912023 likely benign Familial hypercholesterolemia 2017-12-12 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001143745 SCV001304296 uncertain significance Familial hypercholesterolemia 2 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000508963 SCV001361219 likely benign not specified 2019-04-29 criteria provided, single submitter clinical testing Variant summary: APOB c.10520G>C (p.Arg3507Pro) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00019 in 250588 control chromosomes. The observed variant frequency is approximately 6 fold of the estimated maximal expected allele frequency for a pathogenic variant in APOB causing Familial Defective Apolipoprotein B-100 phenotype (3.1e-05), strongly suggesting that the variant is benign. c.10520G>C has been reported in individuals in the literature, however it is reported in association with hypo-betalipoproteinemia despite in vitro evidence that shows the variant to cause reduced binding of LDL to LDLR (Benn_2005). This report does not provide unequivocal conclusions about association of the variant with Familial Defective Apolipoprotein B-100. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as likely benign.
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde,Academisch Medisch Centrum RCV000508963 SCV000605968 benign not specified no assertion criteria provided research

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