ClinVar Miner

Submissions for variant NM_000086.2(CLN3):c.392G>A (p.Ser131Asn) (rs144770450)

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 RCV000187030 SCV000240603 uncertain significance not provided 2018-11-16 criteria provided, single submitter clinical testing The S131N variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. A different missense variant at the same position (S131R) has been reported previously in siblings with cone-rod dystrophy who also had a second CLN3 variant identified on the other allele (Wang et al., 2014). The S131N variant was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. The S131N variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Illumina Clinical Services Laboratory,Illumina RCV000405250 SCV000396333 uncertain significance Neuronal Ceroid-Lipofuscinosis, Dominant/Recessive 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000697965 SCV000826601 uncertain significance Neuronal ceroid lipofuscinosis 2019-01-05 criteria provided, single submitter clinical testing This sequence change replaces serine with asparagine at codon 131 of the CLN3 protein (p.Ser131Asn). The serine residue is weakly conserved and there is a small physicochemical difference between serine and asparagine. This variant is present in population databases (rs144770450, ExAC 0.04%). This variant has not been reported in the literature in individuals with CLN3-related disease. ClinVar contains an entry for this variant (Variation ID: 205109). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000720089 SCV000850965 uncertain significance Seizures 2017-06-29 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Fulgent Genetics,Fulgent Genetics RCV000765282 SCV000896535 uncertain significance Juvenile neuronal ceroid lipofuscinosis 2018-10-31 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.