Submissions for variant NM_017882.3(CLN6):c.890del (p.Pro297fs)

dbSNP: rs154774639

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000669748	SCV000794529	likely pathogenic	Ceroid lipofuscinosis, neuronal, 6A	2017-09-28	criteria provided, single submitter	clinical testing
Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center	RCV000058914	SCV001430898	pathogenic	not provided	2020-07-14	criteria provided, single submitter	clinical testing	PVS1, PM2, PM3
Invitae	RCV002514294	SCV003442957	pathogenic	Neuronal ceroid lipofuscinosis	2023-09-08	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the CLN6 protein in which other variant(s) (p.Pro299Leu) have been determined to be pathogenic (PMID: 19135028). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 68098). This premature translational stop signal has been observed in individual(s) with neuronal ceroid lipofuscinosis (PMID: 21549341). This variant is present in population databases (rs154774639, gnomAD 0.003%). This sequence change creates a premature translational stop signal (p.Pro297Leufs*53) in the CLN6 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 15 amino acid(s) of the CLN6 protein.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV002514294	SCV004039483	likely pathogenic	Neuronal ceroid lipofuscinosis	2023-08-14	criteria provided, single submitter	clinical testing	Variant summary: CLN6 c.890delC (p.Pro297LeufsX53) causes a frameshift which alters the last 15 amino acids and results in an extension of the protein. A missense variant downstream of this position (p.Pro299Leu) has been classified as pathogenic/likely pathogenic by ClinVar submitters with clinical evidence, suggesting this may be a clinically important region of the protein. The variant allele was found at a frequency of 1.2e-05 in 251320 control chromosomes (gnomAD). c.890delC has been reported in the literature in individuals affected with Neuronal Ceroid-Lipofuscinosis (Arsov_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. The following publication has been ascertained in the context of this evaluation (PMID: 21549341). Three submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
SNPedia	RCV000058914	SCV000090435	not provided	not provided		no assertion provided	not provided