ClinVar Miner

Submissions for variant NM_000384.3(APOB):c.2096C>T (p.Pro699Leu) (rs776107514)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Stanford Center for Inherited Cardiovascular Disease,Stanford University RCV000786345 SCV000925123 likely pathogenic not provided 2016-08-16 no assertion criteria provided provider interpretation p.Pro699Leu (c.2096C>T) in the LDLR gene (NM_000527.4) Given sufficient case data we consider this variant likely pathogenic and we do feel it is suitable for assessing risk in healthy relatives ("predictive genetic testing"). The variant has been seen in at least ten unrelated cases of FH (not including this patient's family) giving us significant case data on this variant. In some of the publications it's also listed as Pro678Leu. See the following studies: PMIDs 21642693, 7489239, 23375686, 22390909, 21310417, 26892515). In silico analysis with PolyPhen-2 predicts the variant to be disease causing. The Pro at codon 699 is conserved across species (with the exception of C. eligans), as are neighboring amino acids. There are two individuals with variation at codon 699 listed in the Exome Aggregation Consortium dataset (http://exac.broadinstitute.org/), which currently includes variant calls on ~64,000 individuals of European, African, Latino and Asian descent (as of August 17, 2016). However, the Exac dataset is enriched with CAD cases and it's likely some individuals had FH.

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