ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.367T>C (p.Ser123Pro) (rs879254495)

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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 RCV000237827 SCV000294662 likely benign Familial hypercholesterolemia 1 2016-03-25 criteria provided, single submitter literature only
Invitae RCV001042933 SCV001206642 uncertain significance Familial hypercholesterolemia 2019-01-16 criteria provided, single submitter clinical testing This sequence change replaces serine with proline at codon 123 of the LDLR protein (p.Ser123Pro). The serine residue is moderately conserved and there is a moderate physicochemical difference between serine and proline. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with familial hypercholesterolemia (PMID: 19446849) and has been reported in combination with another LDLR variant, p.Ser493CysfsX42, in an individual with this disease (PMID: 20045108, 21865347). ClinVar contains an entry for this variant (Variation ID: 251181). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Color Health, Inc RCV001042933 SCV001353457 uncertain significance Familial hypercholesterolemia 2019-12-01 criteria provided, single submitter clinical testing
Laboratory of molecular diagnosis of dyslipidemias, Università egli studi di Napoli Federico II RCV000237827 SCV001653589 likely pathogenic Familial hypercholesterolemia 1 2021-05-24 criteria provided, single submitter clinical testing Reduced activity, in stimulated T- and EBV-transformed B-lymphocytes (with c.1478_1479delCT).

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