ClinVar Miner

Submissions for variant NM_000440.3(PDE6A):c.1705C>A (p.Gln569Lys) (rs139444207)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000153658 SCV000203215 uncertain significance not provided 2014-04-07 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000292173 SCV000454682 likely pathogenic Retinitis pigmentosa 2016-09-02 criteria provided, single submitter clinical testing The PDE6A c.1705C>A (p.Gln569Lys) missense variant has been reported in two studies and is found in a total of five individuals with autosomal recessive retinitis pigmentosa, including one homozygote and four compound heterozygotes (Dryja et al. 1999; Avila-Fernandez 2010). The variant is also found in a heterozygous state in six unaffected relatives of the affected individuals. The p.Gln569Lys variant was absent from 70 controls but is reported at a frequency of 0.00026 in the Latino population of the Exome Aggregation Consortium. Based on the evidence, the p.Gln569Lys variant is classified as likely pathogenic for autosomal recessive retinitis pigmentosa. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Invitae RCV000153658 SCV000948416 pathogenic not provided 2020-09-03 criteria provided, single submitter clinical testing This sequence change replaces glutamine with lysine at codon 569 of the PDE6A protein (p.Gln569Lys). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and lysine. This variant is present in population databases (rs139444207, ExAC 0.03%). This variant has been observed to segregate with retinitis pigmentosa in families (PMID: 10393062, 21151602, 29343940). ClinVar contains an entry for this variant (Variation ID: 167431). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Benign; Align-GVGD: Class C4). For these reasons, this variant has been classified as Pathogenic. 5
Ocular Genomics Institute, Massachusetts Eye and Ear RCV001376415 SCV001573544 likely pathogenic Retinitis pigmentosa 43 2021-04-08 criteria provided, single submitter research The PDE6A c.1705C>A variant was identified in an individual with retinitis pigmentosa with a presumed recessive inheritance pattern. Through a review of available evidence we were able to apply the following criteria: PS1, PM2, PP3. Based on this evidence we have classified this variant as Likely Pathogenic.
GeneDx RCV000153658 SCV001829581 pathogenic not provided 2021-03-04 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 33576794, 30998820, 33057649, 31736247, 26806561, 29343940, 31049658, 10393062, 30337596, 21151602)
Broad Institute Rare Disease Group, Broad Institute RCV000292173 SCV001950309 likely pathogenic Retinitis pigmentosa 2021-04-01 criteria provided, single submitter curation The p.Gln569Lys variant in PDE6A was identified in an individual with Retinitis pigmentosa, via a collaborative study between the Broad Institute's Center for Mendelian Genomics and the Pierce lab (https://oculargenomics.meei.harvard.edu/labs/pierce-lab/lab-members/). Through a review of available evidence we were able to apply the following criteria: PS1, PM2. PP3. Based on this evidence we have classified this variant as Likely Pathogenic. If you have any questions about the classification please reach out to the Pierce Lab.

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