ClinVar Miner

Submissions for variant NM_000384.3(APOB):c.11257T>C (p.Phe3753Leu) (rs61741974)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000270662 SCV000426973 likely benign Familial hypercholesterolemia 2 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Clinical Services Laboratory,Illumina RCV000325685 SCV000426974 uncertain significance Hypobetalipoproteinemia, familial, 1 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
GeneDx RCV000419673 SCV000534279 uncertain significance not provided 2016-12-16 criteria provided, single submitter clinical testing The F3753L variant in the APOB gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. Although not present in the homozygous state, the NHLBI ESP Exome Sequencing Project reports F3753L was observed with a frequency of 0.77% (34/4406 alleles) in individuals of African American background, indicating it may be a rare variant in this population. The F3753L variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved, and in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret F3753L as a variant of uncertain significance.
Invitae RCV001085789 SCV000659251 benign Familial hypercholesterolemia 2; Hypobetalipoproteinemia, familial, 1 2019-12-31 criteria provided, single submitter clinical testing
Color RCV000776251 SCV000911503 likely benign Familial hypercholesterolemia 2018-03-26 criteria provided, single submitter clinical testing

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