ClinVar Miner

Submissions for variant NM_000409.4(GUCA1A):c.296A>G (p.Tyr99Cys) (rs104893967)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000414574 SCV000490545 pathogenic not provided 2018-12-27 criteria provided, single submitter clinical testing The Y99C pathogenic variant in the GUCA1A gene has been reported in a family diagnosed with autosomal dominant cone dystrophy (Payne et al., 1998). In vivo functional studies suggest that the Y99C pathogenic variant results in a gain of function of the guanylate cyclase-activating protein, which raises free cGMP levels and elevates cytosolic calcium, resulting in photoreceptor degeneration (Dizhoor et al., 1998; Olshevskaya et al., 2004; Stockman et al., 2014). The Y99C pathogenic variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Therefore, we interpret Y99C to be a pathogenic variant.
NIHR Bioresource Rare Diseases,University of Cambridge RCV000504789 SCV000599090 likely pathogenic Macular dystrophy 2015-01-01 no assertion criteria provided research
NIHR Bioresource Rare Diseases,University of Cambridge RCV000504977 SCV000599091 likely pathogenic Retinitis pigmentosa 2015-01-01 no assertion criteria provided research
OMIM RCV000009721 SCV000029939 pathogenic Cone dystrophy 3 2005-08-01 no assertion criteria provided literature only

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