ClinVar Miner

Submissions for variant NM_174936.4(PCSK9):c.1247T>C (p.Ile416Thr)

gnomAD frequency: 0.00001  dbSNP: rs1343534206
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV000772188 SCV000905305 uncertain significance Familial hypercholesterolemia 2023-12-05 criteria provided, single submitter clinical testing Variant of Uncertain Significance due to insufficient evidence: This variant is a missense variant located in the catalytic peptidase domain of the PCSK9 protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant on the protein function. Computational splicing tools suggest that this variant may not impact the RNA splicing. This variant is rare in the general population and has been identified in 2/246074 chromosomes by the Genome Aggregation Database (gnomAD). To our knowledge, functional assays have not been performed for this variant nor has the variant been reported in individuals affected with FH in the literature. Available evidence is insufficient to determine the pathogenicity of this variant conclusively.
Ambry Genetics RCV004027240 SCV003742053 uncertain significance Cardiovascular phenotype 2024-11-21 criteria provided, single submitter clinical testing The c.1247T>C (p.I416T) alteration is located in exon 8 (coding exon 8) of the PCSK9 gene. This alteration results from a T to C substitution at nucleotide position 1247, causing the isoleucine (I) at amino acid position 416 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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