ClinVar Miner

Submissions for variant NM_000384.3(APOB):c.10385A>G (p.Tyr3462Cys) (rs200305144)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color RCV000771604 SCV000904208 likely benign Familial hypercholesterolemia 2018-03-19 criteria provided, single submitter clinical testing
Invitae RCV000865956 SCV001006986 benign Familial hypercholesterolemia 2; Hypobetalipoproteinemia, familial, 1 2019-12-31 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV001192835 SCV001361218 likely benign not specified 2019-04-16 criteria provided, single submitter clinical testing Variant summary: APOB c.10385A>G (p.Tyr3462Cys) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00016 in 253350 control chromosomes, predominantly at a frequency of 0.0035 within the Ashkenazi Jewish subpopulation in the gnomAD database. The observed variant frequency within Ashkenazi Jewish control individuals in the gnomAD database is approximately 112 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 a benign polymorphism found primarily in populations of Ashkenazi Jewish origin. c.10385A>G has been reported in the literature in an individual affected with hypertriglyceridemia (Johansen_2010). However, this report does not provide unequivocal conclusions about association of the variant with Familial Defective Apolipoprotein B-100. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely benign.

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