ClinVar Miner

Submissions for variant NM_001909.5(CTSD):c.592A>G (p.Ile198Val)

gnomAD frequency: 0.00011  dbSNP: rs556334193
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000632710 SCV000753896 uncertain significance Neuronal ceroid lipofuscinosis 2022-09-13 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 198 of the CTSD protein (p.Ile198Val). This variant is present in population databases (rs556334193, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with CTSD-related conditions. ClinVar contains an entry for this variant (Variation ID: 527749). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CTSD protein function. 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.
GeneDx RCV001560644 SCV001783099 uncertain significance not provided 2023-07-12 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV002358771 SCV002647507 uncertain significance Inborn genetic diseases 2018-07-27 criteria provided, single submitter clinical testing The p.I198V variant (also known as c.592A>G), located in coding exon 5 of the CTSD gene, results from an A to G substitution at nucleotide position 592. The isoleucine at codon 198 is replaced by valine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
New York Genome Center RCV001255002 SCV001431091 uncertain significance Seizure; Intellectual disability 2020-03-09 no assertion criteria provided clinical testing

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