ClinVar Miner

Submissions for variant NM_174936.4(PCSK9):c.97G>A (p.Asp33Asn)

gnomAD frequency: 0.00001  dbSNP: rs917219621
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001190553 SCV001358059 uncertain significance Familial hypercholesterolemia 2023-12-05 criteria provided, single submitter clinical testing This missense variant replaces aspartic acid with asparagine at codon 33 of the PCSK9 protein. Computational prediction tools and conservation analyses suggest that this variant may not impact the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with familial hypercholesterolemia in the literature. This variant has been identified in 1/183184 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV001876229 SCV002304609 uncertain significance Hypercholesterolemia, autosomal dominant, 3 2023-03-04 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 33 of the PCSK9 protein (p.Asp33Asn). This variant is present in population databases (no rsID available, gnomAD 0.004%). This missense change has been observed in individual(s) with clinical features of familial hypercholesterolemia (Invitae). ClinVar contains an entry for this variant (Variation ID: 927338). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PCSK9 protein function. 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.
All of Us Research Program, National Institutes of Health RCV001876229 SCV005431351 uncertain significance Hypercholesterolemia, autosomal dominant, 3 2024-08-06 criteria provided, single submitter clinical testing This missense variant replaces aspartic acid with asparagine at codon 33 of the PCSK9 protein. Computational prediction tools and conservation analyses suggest that this variant may not impact the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with familial hypercholesterolemia in the literature. This variant has been identified in 1/183184 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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