Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000522018 | SCV000616957 | uncertain significance | not provided | 2018-06-15 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the CTSD gene. The T30M variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The T30M variant is observed in 1/22284 (0.005%) alleles from individuals of European background (Lek et al., 2016). The T30M 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; 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 variant or a rare benign variant. |
Invitae | RCV001060632 | SCV001225336 | uncertain significance | Neuronal ceroid lipofuscinosis | 2022-09-01 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 30 of the CTSD protein (p.Thr30Met). This variant is present in population databases (rs747274524, gnomAD 0.004%). 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: 449144). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably 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 | RCV002376959 | SCV002683743 | uncertain significance | Inborn genetic diseases | 2017-10-12 | criteria provided, single submitter | clinical testing | The p.T30M variant (also known as c.89C>T), located in coding exon 2 of the CTSD gene, results from a C to T substitution at nucleotide position 89. The threonine at codon 30 is replaced by methionine, an amino acid with similar properties. This amino acid position is not well 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. |