Submissions for variant NM_017882.3(CLN6):c.791CCT[1] (p.Ser265del)

dbSNP: rs768422260

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000187114	SCV000240689	uncertain significance	not specified	2014-11-18	criteria provided, single submitter	clinical testing	c.794_796delCCT: p.Ser265del (S265del) in exon 7 of the CLN6 gene (NM_017882.2) The normal sequence with the bases that are deleted in braces is: TCCT{CCT}TCGC. The c.794_796delCCT variant has been reported previously in an individual with late-infantile neuronal ceroid lipofuscinosis (Sharp et al., 2003). The c.794_796delCCT variant results in an in-frame deletion of a single Serine residue at a conserved position in the seventh transmembrane domain of the CLN6 protein (Kousi et al., 2012). However, this deletion is not expected to result in protein truncation or nonsense-mediated mRNA decay. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in PME-EPI,CHILD-EPI panel(s).
Genetic Services Laboratory, University of Chicago	RCV000195031	SCV000247045	pathogenic	Ceroid lipofuscinosis, neuronal, 6A	2015-05-11	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000727479	SCV000708915	uncertain significance	not provided	2017-06-13	criteria provided, single submitter	clinical testing
Mendelics	RCV000989353	SCV001139644	pathogenic	Neuronal ceroid lipofuscinosis	2019-05-28	criteria provided, single submitter	clinical testing
Invitae	RCV000989353	SCV001410001	pathogenic	Neuronal ceroid lipofuscinosis	2024-01-22	criteria provided, single submitter	clinical testing	This variant, c.794_796del, results in the deletion of 1 amino acid(s) of the CLN6 protein (p.Ser265del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs768422260, gnomAD 0.01%). This variant has been observed in individuals with neuronal ceroid lipofuscinosis type 6 (PMID: 19135028, 19520283, 30705896, 31029456). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 205182). 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 are conflicting or provide insufficient evidence to determine the effect of this variant on CLN6 function (PMID: 15265688). For these reasons, this variant has been classified as Pathogenic.
Centre for Inherited Metabolic Diseases, Karolinska University Hospital	RCV000195031	SCV001571377	pathogenic	Ceroid lipofuscinosis, neuronal, 6A	2021-04-13	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000727479	SCV001713713	uncertain significance	not provided	2019-04-07	criteria provided, single submitter	clinical testing
Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India	RCV000195031	SCV001786701	likely pathogenic	Ceroid lipofuscinosis, neuronal, 6A		criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000727479	SCV002023253	likely pathogenic	not provided	2020-11-23	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV001810435	SCV002060242	pathogenic	Ceroid lipofuscinosis, neuronal, 6A; Ceroid lipofuscinosis, neuronal, 6B (Kufs type)	2021-11-10	criteria provided, single submitter	clinical testing	NM_017882.2(CLN6):c.794_796delCCT(S265del) is an in-frame deletion variant classified as pathogenic in the context of neuronal ceroid lipofuscinosis, CLN6-related. S265del has been observed in cases with relevant disease (PMID: 21990111, 12815591, 19135028, 29930972). Functional assessments of this variant are available in the literature (PMID: 19135028, 15265688). S265del has been observed in population frequency databases (gnomAD: AFR 0.01%). In summary, NM_017882.2(CLN6):c.794_796delCCT(S265del) is an in-frame deletion variant that has been observed more frequently in cases with the relevant disease than in healthy populations. Please note: this variant was assessed in the context of healthy population screening.
CeGaT Center for Human Genetics Tuebingen	RCV000727479	SCV002497797	pathogenic	not provided	2023-03-01	criteria provided, single submitter	clinical testing	CLN6: PP4:Strong, PM2, PM3, PM4
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV000195031	SCV004806445	likely pathogenic	Ceroid lipofuscinosis, neuronal, 6A	2024-03-25	criteria provided, single submitter	clinical testing