ClinVar Miner

Submissions for variant NM_000440.3(PDE6A):c.1407G>C (p.Leu469Phe)

gnomAD frequency: 0.00001  dbSNP: rs727504073
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000153660 SCV000203217 uncertain significance not provided 2013-12-27 criteria provided, single submitter clinical testing
Blueprint Genetics RCV001075505 SCV001241129 uncertain significance Retinal dystrophy 2018-11-08 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000153660 SCV001378855 uncertain significance not provided 2024-04-16 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 469 of the PDE6A protein (p.Leu469Phe). This variant also falls at the last nucleotide of exon 10, which is part of the consensus splice site for this exon. This variant is present in population databases (rs727504073, gnomAD 0.003%). This missense change has been observed in individual(s) with retinitis pigmentosa (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 167433). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.
GeneDx RCV000153660 SCV003926209 uncertain significance not provided 2022-11-16 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; In addition, in silico splice predictors suggest this variant may lead to abnormal gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; Has not been previously published in the peer-reviewed literature as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: Pascual2018[Thesis])
Breakthrough Genomics, Breakthrough Genomics RCV000153660 SCV005188676 uncertain significance not provided criteria provided, single submitter not provided

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