ClinVar Miner

Submissions for variant NM_001909.5(CTSD):c.52G>C (p.Ala18Pro) (rs796052403)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000187311 SCV000240893 uncertain significance not provided 2015-08-20 criteria provided, single submitter clinical testing p.Ala18Pro (GCC>CCC): c.52 G>C in exon 1 of the CTSD gene (NM_001909.4)A variant of unknown significance has been identified in the CTSD gene. The A18P variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 4,200 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The A18P variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some 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 INFANTV2-EPIV2-1 panel(s).
Invitae RCV000687303 SCV000814863 uncertain significance Neuronal ceroid lipofuscinosis 2020-04-23 criteria provided, single submitter clinical testing This sequence change replaces alanine with proline at codon 18 of the CTSD protein (p.Ala18Pro). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and proline. While this variant is not present in population databases, the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with CTSD-related disease. ClinVar contains an entry for this variant (Variation ID: 205354). 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 RCV000718706 SCV000849570 uncertain significance Seizures 2019-04-03 criteria provided, single submitter clinical testing The p.A18P variant (also known as c.52G>C), located in coding exon 1 of the CTSD gene, results from a G to C substitution at nucleotide position 52. The alanine at codon 18 is replaced by proline, an amino acid with highly similar properties. This amino acid position is poorly 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.

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