ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.1330T>C (p.Ser444Pro)

dbSNP: rs875989919
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
LDLR-LOVD, British Heart Foundation RCV000211635 SCV000295373 likely pathogenic Hypercholesterolemia, familial, 1 2016-03-25 criteria provided, single submitter literature only
GeneDx RCV000497836 SCV000589575 likely pathogenic not provided 2017-06-08 criteria provided, single submitter clinical testing The S444P variant (reported as S423P due to historic nomenclature) has been reported previously in a few unrelated individuals with familial hypercholesterolemia, two of whom harbored a second LDLR variant (Laurie et al., 2004; Kusters et al., 2013). The S444P variant is not observed in large population cohorts (Lek et al., 2016). The S444P variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs within the LDL-receptor class B 2 repeat region. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. We interpret S444P as a likely pathogenic variant.
Cardiovascular Genetics Laboratory, PathWest Laboratory Medicine WA - Fiona Stanley Hospital RCV000211635 SCV000268611 pathogenic Hypercholesterolemia, familial, 1 2008-06-09 no assertion criteria provided clinical testing
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum RCV000211635 SCV000606398 pathogenic Hypercholesterolemia, familial, 1 no assertion criteria provided research

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