ClinVar Miner

Submissions for variant NM_000180.4(GUCY2D):c.2618C>G (p.Pro873Arg)

dbSNP: rs1567961680
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Blueprint Genetics RCV001074400 SCV001239980 pathogenic Retinal dystrophy 2019-08-09 criteria provided, single submitter clinical testing
3billion RCV002250683 SCV002521467 pathogenic Night blindness, congenital stationary, type1i 2022-05-22 criteria provided, single submitter clinical testing The variant is not observed in the gnomAD v2.1.1 dataset. Functional studies provide strong evidence of the variant having a damaging effect on the gene or gene product (PMID:30319355). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.74; 3Cnet: 0.21). Same nucleotide change resulting in same amino acid change has been previously reported to be associated with GUCY2D related disorder (ClinVar ID: VCV000575081 / PMID: 30319355). The variant has been reported to co-segregate with the disease in at least 3 similarly affected relatives/individuals in the same family or similarly affected unrelated family (PMID:30319355). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.
Labcorp Genetics (formerly Invitae), Labcorp RCV000697191 SCV000825788 uncertain significance Cone-rod dystrophy 6; Leber congenital amaurosis 1 2018-06-13 flagged submission clinical testing 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with GUCY2D-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with arginine at codon 873 of the GUCY2D protein (p.Pro873Arg). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and arginine.
Sharon lab, Hadassah-Hebrew University Medical Center RCV002267739 SCV001161103 likely pathogenic Cone-rod dystrophy 2019-06-23 no assertion criteria provided research

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