ClinVar Miner

Submissions for variant NM_006493.4(CLN5):c.188G>A (p.Arg63His) (rs104894386)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000698933 SCV000827624 likely pathogenic Neuronal ceroid lipofuscinosis 2019-04-30 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 112 of the CLN5 protein (p.Arg112His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs104894386, ExAC 0.006%). This variant has been observed to segregate with juvenile onset neuronal ceroid lipofuscinosis in a family (PMID: 15728307, 30078242). ClinVar contains an entry for this variant (Variation ID: 2567). Experimental studies have shown that this missense change disturbs the lysosomal trafficking of the protein (PMID: 20052765). 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: 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.
OMIM RCV000002676 SCV000022834 pathogenic Neuronal ceroid lipofuscinosis 5 2005-02-22 no assertion criteria provided literature only

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