Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001266535 | SCV001444711 | likely pathogenic | Inborn genetic diseases | 2020-01-30 | criteria provided, single submitter | clinical testing | The alteration results in an amino acid change: The c.449G>T (p.R150I) alteration is located in exon 6 (coding exon 5) of the TAOK1 gene. This alteration results from a G to T substitution at nucleotide position 449. This change occurs in the last base pair of coding exon 5, which makes it likely to have some effect on normal mRNA splicing. In addition to potential splicing impact, this alteration causes the arginine (R) at amino acid position 150 to be replaced by an isoleucine (I). The alteration is not observed in population databases: Based on data from the Genome Aggregation Database (gnomAD), the TAOK1 c.449G>T alteration was not observed, with coverage at this position. The altered nucleotide is conserved throughout evolution: The c.449G nucleotide is conserved in available vertebrate species. The amino acid is located in a functionally important protein domain: The p.R150 amino acid is located in the conserved kinase domain, also known as catalytic domain, of the TAOK1 protein. The catalytic domains of protein kinases contain 12 conserved subdomains that fold into a common catalytic core structure. R150 is part of the catalytic loop of subdomain VIB and adjacent to residue D151, which is likely important for the catalytic activity of that region (Hanks, 1995). The alteration is predicted deleterious by in silico modeling: The p.R150I amino acid change is predicted to be deleterious by in silico analysis. Additionally, this nucleotide change is predicted to weaken the native splice donor site based on the BDGP and ESEfinder splice site in silico tools; however, direct evidence is unavailable. Based on the available evidence, this alteration is classified as likely pathogenic. |
| OMIM | RCV003229036 | SCV001981602 | pathogenic | DEVELOPMENTAL DELAY WITHOUT INTELLECTUAL IMPAIRMENT OR BEHAVIORAL ABNORMALITIES | 2023-05-22 | no assertion criteria provided | literature only |