ClinVar Miner

Submissions for variant NM_000384.3(APOB):c.649C>T (p.Pro217Ser)

dbSNP: rs573308525
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
New York Genome Center RCV002468034 SCV002764477 uncertain significance Hypercholesterolemia, autosomal dominant, type B; Familial hypobetalipoproteinemia 1 2021-12-20 criteria provided, single submitter clinical testing The heterozygous c.649C>T (p.Pro217Ser) missense variant identified in the APOB gene has not been reported in affected individuals in the literature. The variant has 0.00003285 allele frequency in the gnomAD(v3) database (5 out of 152218 heterozygous alleles, no homozygotes) suggesting it is not a common benign variant in the populations represented in that database. This variant has been reported in the ClinVar database as a ‘variant of uncertain significance’[Variation ID: 630360] in the context of familial Hypercholesterolemia. The variant affects a moderately conserved residue and multiple in silico prediction tools provide conflicting predictions about potential pathogenicity of this variant (CADD=22.2, REVEL score = 0.251). Additionally, another missense substitution affecting this protein residue p.Pro217His was previously identified in a patient of Chinese origin with severe hypertriglyceridemia as a Variant of Uncertain Significance [PMID:30420299]. Based on the available evidence, the heterozygous c.649C>T (p.Pro217Ser) variant identified in the APOB gene is reported as aVariant of Uncertain Significance.
Invitae RCV002468034 SCV003517384 likely benign Hypercholesterolemia, autosomal dominant, type B; Familial hypobetalipoproteinemia 1 2024-01-31 criteria provided, single submitter clinical testing

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