ClinVar Miner

Submissions for variant NM_006493.4(CLN5):c.869G>T (p.Arg290Ile)

gnomAD frequency: 0.00003  dbSNP: rs770688728
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000483654 SCV000571671 uncertain significance not provided 2016-09-13 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the CLN5 gene. The R339I variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It 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. The R339I variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this substitution occurs at a position that is not conserved. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000814083 SCV000954480 uncertain significance Neuronal ceroid lipofuscinosis 2022-07-13 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with isoleucine, which is neutral and non-polar, at codon 339 of the CLN5 protein (p.Arg339Ile). This variant is present in population databases (rs770688728, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with CLN5-related conditions. ClinVar contains an entry for this variant (Variation ID: 422251). 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 C0"). 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.
Genome-Nilou Lab RCV001785630 SCV002027075 uncertain significance Neuronal ceroid lipofuscinosis 5 2021-09-05 criteria provided, single submitter clinical testing
Natera, Inc. RCV000814083 SCV002087981 uncertain significance Neuronal ceroid lipofuscinosis 2020-08-28 no assertion criteria provided clinical testing

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