ClinVar Miner

Submissions for variant NM_001122769.3(LCA5):c.2006G>A (p.Arg669Lys)

dbSNP: rs371733166
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001000884 SCV001157966 uncertain significance Leber congenital amaurosis 5 2019-01-03 criteria provided, single submitter clinical testing The LCA5 c.2006G>A; p.Arg669Lys variant (rs371733166), to our knowledge, is not reported in the medical literature or gene-specific databases. The variant is listed in the general population with an allele frequency of 0.0008% (2/251158 alleles) in the Genome Aggregation Database. The arginine at this position is moderately conserved and computational analyses (PolyPhen-2, SIFT) predict this variant is deleterious. However, most pathogenic LCA5 variants are truncating (Mackay 2013). Considering available information, the clinical significance of this variant cannot be determined with certainty. References: Mackay DS et al. Screening of a large cohort of leber congenital amaurosis and retinitis pigmentosa patients identifies novel LCA5 mutations and new genotype-phenotype correlations. Hum Mutat. 2013 Nov;34(11):1537-1546.
Labcorp Genetics (formerly Invitae), Labcorp RCV001349643 SCV001543998 uncertain significance not provided 2024-06-17 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 669 of the LCA5 protein (p.Arg669Lys). This variant is present in population databases (no rsID available, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with LCA5-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The lysine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
Ambry Genetics RCV004986732 SCV005607992 uncertain significance Inborn genetic diseases 2024-10-21 criteria provided, single submitter clinical testing The c.2006G>A (p.R669K) alteration is located in exon 9 (coding exon 7) of the LCA5 gene. This alteration results from a G to A substitution at nucleotide position 2006, causing the arginine (R) at amino acid position 669 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001000884 SCV002076744 uncertain significance Leber congenital amaurosis 5 2020-09-23 no assertion criteria provided clinical testing

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