Description
The p.T353N variant (also known as c.1058C>A), located in coding exon 8 of the TPP1 gene, results from a C to A substitution at nucleotide position 1058. The threonine at codon 353 is replaced by asparagine, an amino acid with similar properties. There is a known pathogenic mutation, p.T353P (c.1057A>C), located at the same position as this alteration, which has been detected in conjunction with another CLN6 mutation in two individuals with late-infantile neuronal ceroid lipofuscinosis (Steinfeld R et al. Am. J. Med. Genet., 2002 Nov;112:347-54). In addition, the p.T353P mutation has been shown by structural and functional studies to induce folding defects; however, this mutation is significantly more destabilizing than the p.T353N variant (Steinfeld R et al. Hum. Mol. Genet., 2004 Oct;13:2483-91). This variant was previously reported in the SNPDatabase as rs145966505. Based on data from the NHLBI Exome Sequencing Project (ESP), the A allele has an overall frequency of approximately 0.02% (2/12994) total alleles studied, having been observed in 0.05% (2/4402) African American alleles. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
# | Sample | Method | Observation |
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Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
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1 | germline | unknown | 1 | not provided | not provided | | 1 | not provided | not provided | not provided |