ClinVar Miner

Submissions for variant NM_000086.2(CLN3):c.944dup (p.His315fs) (rs386833740)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000477605 SCV000549229 pathogenic Neuronal ceroid lipofuscinosis 2020-08-29 criteria provided, single submitter clinical testing This sequence change inserts 1 nucleotide in exon 13 of the CLN3 mRNA (c.944dupA), causing a frameshift at codon 315. This creates a premature translational stop signal (p.His315Glnfs*67) and is expected to result in an absent or disrupted protein product. Loss-of-function variants in CLN3 are known to be pathogenic. This particular variant has been reported in individuals affected with juvenile neuronal ceroid lipofuscinoses (PMID: 9311735, 23374165). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000049704 SCV000917247 pathogenic Neuronal ceroid lipofuscinosis 3 2017-11-13 criteria provided, single submitter clinical testing Variant summary: The CLN3 c.944dupA (p.His315GlufsX67) variant results in a premature termination codon, predicted to cause a truncated or absent CLN3 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. One in silico tool predicts a damaging outcome for this variant. This variant was found in 1/245564 control chromosomes (gnomAD) at a frequency of 0.0000041, which does not exceed the estimated maximal expected allele frequency of a pathogenic CLN3 variant (0.0006124). The variant has been reported in affected individuals in the literature (Munroe_1997, Santorelli_2013, Kwon_2011). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic/likely pathogenic. Taken together, this variant is classified as pathogenic.
Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM) RCV000049704 SCV000082111 probable-pathogenic Neuronal ceroid lipofuscinosis 3 no assertion criteria provided not provided Converted during submission to Likely pathogenic.
Counsyl RCV000049704 SCV001132154 pathogenic Neuronal ceroid lipofuscinosis 3 2018-01-10 no assertion criteria provided clinical testing

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