ClinVar Miner

Submissions for variant NM_000384.3(APOB):c.5566_5567del (p.Val1856fs)

dbSNP: rs121918384
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002513122 SCV003287851 pathogenic Hypercholesterolemia, autosomal dominant, type B; Familial hypobetalipoproteinemia 1 2022-03-08 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 17884). This premature translational stop signal has been observed in individual(s) with hypobetalipoproteinemia (PMID: 2614276). This variant is present in population databases (rs121918384, gnomAD 0.007%). This sequence change creates a premature translational stop signal (p.Val1856Cysfs*2) in the APOB gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in APOB are known to be pathogenic (PMID: 20032471).
Clinical Genomics Laboratory, Washington University in St. Louis RCV002513122 SCV005685475 likely pathogenic Hypercholesterolemia, autosomal dominant, type B; Familial hypobetalipoproteinemia 1 2024-10-04 criteria provided, single submitter clinical testing The APOB c.5566_5567del (p.Val1856Cysfs*2) variant has been reported in four individuals affected by hypobetalipoproteinemia. Among these individuals, three were compound heterozygous for this variant and another pathogenic or likely pathogenic variant, while one individual with lower circulating APOB levels was heterozygous for this variant (Talmud P et al., PMID: 2614276; Zheng M et al., PMID: 36937991). This variant has been reported in the ClinVar database as a pathogenic variant by two submitters. This variant causes a frameshift by deleting two nucleotides, leading to a premature termination codon, which is predicted to lead to nonsense mediated decay. This variant is only observed on 1 out of 251,300 alleles in the general population (gnomAD v.2.1.1), indicating it is not a common variant. Based on available information and the ACMG/AMP guidelines for variant interpretation (Richards S et al., PMID: 25741868), this variant is classified as likely pathogenic.
OMIM RCV000019473 SCV000039764 pathogenic Familial hypobetalipoproteinemia 1992-08-01 no assertion criteria provided literature only

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