ClinVar Miner

Submissions for variant NM_006493.4(CLN5):c.187C>T (p.Arg63Cys) (rs786205211)

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Total submissions: 4
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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 2019-05-27 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 112 of the CLN5 protein (p.Arg112Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to segregate with late infantile neuronal ceroid lipofuscinosis in a family (PMID: 30078242). ClinVar contains an entry for this variant (Variation ID: 190222). 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 disrupts the p.Arg112 amino acid residue in CLN5. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 15728307, 30078242, 20052765). 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.
Nilou-Genome Lab RCV000170441 SCV001977457 likely pathogenic Neuronal ceroid lipofuscinosis 5 2021-08-10 criteria provided, single submitter clinical testing
Mendelics RCV000170441 SCV000222879 likely pathogenic Neuronal ceroid lipofuscinosis 5 2015-02-14 no assertion criteria provided clinical testing

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