ClinVar Miner

Submissions for variant NM_001042432.2(CLN3):c.949C>T (p.Gln317Ter)

gnomAD frequency: 0.00001  dbSNP: rs796052335
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000187013 SCV000240586 pathogenic not provided 2014-04-18 criteria provided, single submitter clinical testing p.Gln317Stop (CAG>TAG): c.949 C>T in exon 13 of the CLN3 gene (NM_001042432.1) The Q317X nonsense mutation in the CLN3 gene is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Although this mutation has not been reported previously to our knowledge, it is considered a disease-causing mutation. The variant is found in EPILEPSY panel(s).
Genome-Nilou Lab RCV001729442 SCV001977442 pathogenic Neuronal ceroid lipofuscinosis 3 2021-08-10 criteria provided, single submitter clinical testing
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute RCV001729442 SCV002557849 pathogenic Neuronal ceroid lipofuscinosis 3 2022-02-02 criteria provided, single submitter clinical testing Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with neuronal ceroid lipofuscinosis, 3 (MIM#204200) and nonsyndromic retinal degeneration (PMID: 31568712). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0252 - This variant is homozygous. (I) 0304 - Variant is present in gnomAD <0.01 for a recessive condition (v3: 1 heterozygote, 0 homozygotes). (SP) 0701 - Other NMD-predicted variants comparable to the one identified in this case have very strong previous evidence for pathogenicity. There are multiple likely pathogenic and pathogenic NMD-predicted variants that have been described (ClinVar, PMID: 31568712). (SP) 0803 - This variant has limited previous evidence of pathogenicity in an unrelated individual. This variant has been classified once as pathogenic by a clinical diagnostic laboratory (ClinVar). (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign
Labcorp Genetics (formerly Invitae), Labcorp RCV002516983 SCV003312475 pathogenic Neuronal ceroid lipofuscinosis 2023-02-20 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 205092). This variant has not been reported in the literature in individuals affected with CLN3-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln317*) in the CLN3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CLN3 are known to be pathogenic (PMID: 9311735, 28542676).
Fulgent Genetics, Fulgent Genetics RCV001729442 SCV005646531 likely pathogenic Neuronal ceroid lipofuscinosis 3 2024-04-01 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.