ClinVar Miner

Submissions for variant NM_006493.4(CLN5):c.187C>T (p.Arg63Cys)

gnomAD frequency: 0.00001  dbSNP: rs786205211
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000170441 SCV000800605 uncertain significance Neuronal ceroid lipofuscinosis 5 2017-10-16 criteria provided, single submitter clinical testing
Invitae RCV001054069 SCV001218362 likely pathogenic Neuronal ceroid lipofuscinosis 2023-12-17 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 112 of the CLN5 protein (p.Arg112Cys). This variant is present in population databases (rs786205211, gnomAD 0.007%). This missense change has been observed in individual(s) with late infantile neuronal ceroid lipofuscinosis (PMID: 30078242). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 190222). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt CLN5 protein function with a positive predictive value of 80%. This variant disrupts the p.Arg112 amino acid residue in CLN5. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 15728307, 20052765, 30078242). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Genome-Nilou Lab RCV000170441 SCV001977457 likely pathogenic Neuronal ceroid lipofuscinosis 5 2021-08-10 criteria provided, single submitter clinical testing
Ambry Genetics RCV002321680 SCV002606719 uncertain significance Inborn genetic diseases 2018-03-12 criteria provided, single submitter clinical testing The p.R112C variant (also known as c.334C>T), located in coding exon 2 of the CLN5 gene, results from a C to T substitution at nucleotide position 334. The arginine at codon 112 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Mendelics RCV000170441 SCV000222879 likely pathogenic Neuronal ceroid lipofuscinosis 5 2015-02-14 no assertion criteria provided clinical testing

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