ClinVar Miner

Submissions for variant NM_006493.4(CLN5):c.522dup (p.Trp175fs)

gnomAD frequency: 0.00003  dbSNP: rs386833979
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000049956 SCV000486348 likely pathogenic Neuronal ceroid lipofuscinosis 5 2016-05-16 criteria provided, single submitter clinical testing
Invitae RCV000690321 SCV000818003 pathogenic Neuronal ceroid lipofuscinosis 2022-04-16 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Trp224Leufs*30) in the CLN5 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 184 amino acid(s) of the CLN5 protein. This variant is present in population databases (rs770949806, gnomAD 0.007%). This premature translational stop signal has been observed in individual(s) with neuronal ceroid lipofuscinosis (PMID: 21990111; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as c.669insC and p.E253X. ClinVar contains an entry for this variant (Variation ID: 56543). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this premature translational stop signal affects CLN5 function (PMID: 20052765). This variant disrupts a region of the CLN5 protein in which other variant(s) (p.Lys368Serfs*15) have been determined to be pathogenic (PMID: 20157158, 20960652, 22532218, 25976102; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Genome-Nilou Lab RCV000049956 SCV001977481 pathogenic Neuronal ceroid lipofuscinosis 5 2021-08-10 criteria provided, single submitter clinical testing
Baylor Genetics RCV000049956 SCV004214389 pathogenic Neuronal ceroid lipofuscinosis 5 2023-05-17 criteria provided, single submitter clinical testing
Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM) RCV000049956 SCV000082365 probable-pathogenic Neuronal ceroid lipofuscinosis 5 no assertion criteria provided not provided Converted during submission to Likely pathogenic.
Natera, Inc. RCV000690321 SCV002087970 pathogenic Neuronal ceroid lipofuscinosis 2021-08-20 no assertion criteria provided clinical testing

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