Submissions for variant NM_001042432.2(CLN3):c.265C>T (p.Arg89Ter)

dbSNP: rs386833713

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001199876	SCV001370627	likely pathogenic	Neuronal ceroid lipofuscinosis	2020-05-14	criteria provided, single submitter	clinical testing	Variant summary: CLN3 c.265C>T (p.Arg89X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251492 control chromosomes (gnomAD). c.265C>T has been reported in the literature in one homozygous individual affected with Juvenile Neuronal Ceroid-Lipofuscinosis (Juvenile Batten Disease) (Perez-Poyato_2011). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Invitae	RCV001199876	SCV001586095	pathogenic	Neuronal ceroid lipofuscinosis	2023-08-23	criteria provided, single submitter	clinical testing	This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg89*) 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). This premature translational stop signal has been observed in individual(s) with juvenile neuronal ceroid lipofuscinosis (PMID: 21499717). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 56262).
Ambry Genetics	RCV002426609	SCV002744109	pathogenic	Inborn genetic diseases	2015-12-15	criteria provided, single submitter	clinical testing	The p.R89* pathogenic mutation (also known as c.265C>T), located in coding exon 4 of the CLN3 gene, results from a C to T substitution at nucleotide position 265. This changes the amino acid from an arginine to a stop codon within coding exon 4. In one study, this mutation was identified in the homozygous state in an 12 year old male with visual failure, myoclonic generalized seizures, papillary pallor and a diagnosis of classic juvenile neuronal ceroid lipofuscinosis (Pérez-Poyato MS, et al. J. Inherit. Metab. Dis. 2011;34(5):1083-93). In addition to the clinical data presented in the literature, since premature stop codons are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294).
Baylor Genetics	RCV000049674	SCV005058452	pathogenic	Neuronal ceroid lipofuscinosis 3	2024-03-22	criteria provided, single submitter	clinical testing
Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM)	RCV000049674	SCV000082081	probable-pathogenic	Neuronal ceroid lipofuscinosis 3		no assertion criteria provided	not provided	Converted during submission to Likely pathogenic.