ClinVar Miner

Submissions for variant NM_174936.3(PCSK9):c.386A>G (p.Asp129Gly) (rs1553135971)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Cardiovascular Research Group,Instituto Nacional de Saude Doutor Ricardo Jorge RCV000505210 SCV000599422 likely pathogenic Familial hypercholesterolemia 1 2016-03-01 criteria provided, single submitter curation
Invitae RCV000706194 SCV000835232 uncertain significance Familial hypercholesterolemia 3 2018-08-13 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with glycine at codon 129 of the PCSK9 protein (p.Asp129Gly). The aspartic acid residue is highly conserved and there is a moderate physicochemical difference between aspartic acid and glycine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with familial hypercholesterolemia (PMID: 17765244). ClinVar contains an entry for this variant (Variation ID: 438332). Experimental studies have shown that this missense change leads to a gain-of-function effect (PMID: 17765244, 27280970). The observation of one or more missense substitutions at this codon (p.Asp129Gly and p.Asp129Asn) in affected individuals suggests that this may be a clinically significant residue (PMID: 17765244, 19081568). 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.

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