ClinVar Miner

Submissions for variant NM_020366.4(RPGRIP1):c.3553G>A (p.Glu1185Lys)

dbSNP: rs766353935
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001000640 SCV001157660 uncertain significance not specified 2018-07-05 criteria provided, single submitter clinical testing The RPGRIP1 c.3553G>A; p.Glu1185Lys variant, to our knowledge, is not reported in the medical literature or in gene-specific databases. The variant is also absent from general population databases (1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database), indicating it is not a common polymorphism. The glutamic acid at codon 1185 is conserved but computational analyses (SIFT: Tolerated, PolyPhen-2: Possibly Damaging) predict conflicting effects of this variant on protein structure/function. Considering available information, there is insufficient evidence to classify the variant. Pathogenic RPGRIP1 variants are causative for autosomal recessive cone-rod dystrophy (MIM: 608194) or Leber congenital amaurosis (MIM: 613826).
Invitae RCV001869420 SCV002210807 uncertain significance Cone-rod dystrophy 13; Leber congenital amaurosis 6 2021-11-06 criteria provided, single submitter 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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The lysine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 811055). This variant has not been reported in the literature in individuals affected with RPGRIP1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1185 of the RPGRIP1 protein (p.Glu1185Lys).

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