ClinVar Miner

Submissions for variant NM_001909.5(CTSD):c.928G>A (p.Glu310Lys) (rs373699222)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000187297 SCV000240879 uncertain significance not provided 2017-09-11 criteria provided, single submitter clinical testing p.Glu310Lys (GAG>AAG): c.928 G>A in exon 7 of the CTSD gene (NM_001909.4). A variant of unknown significance has been identified in the CTSD gene. The E310K variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The E310K 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 E310K variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this substitution occurs at a position that is not conserved across species, and in silico analysis predicts this variant likely does not alter the protein structure/function. 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 EPILEPSY panel(s).
Invitae RCV000705805 SCV000834820 uncertain significance Neuronal ceroid lipofuscinosis 2019-07-22 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 310 of the CTSD protein (p.Glu310Lys). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs373699222, ExAC 0.002%). This variant has not been reported in the literature in individuals with CTSD-related disease. ClinVar contains an entry for this variant (Variation ID: 205341). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Illumina Clinical Services Laboratory,Illumina RCV001105477 SCV001262445 uncertain significance Neuronal ceroid lipofuscinosis 10 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

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.