Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001218206 | SCV001390078 | pathogenic | Alpha-N-acetylgalactosaminidase deficiency type 1 | 2023-10-13 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Trp148*) in the NAGA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NAGA are known to be pathogenic (PMID: 8782044, 11251574). This variant is present in population databases (rs781137026, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with NAGA-related conditions. ClinVar contains an entry for this variant (Variation ID: 947187). For these reasons, this variant has been classified as Pathogenic. |
| Neuberg Supratech Reference Laboratories Pvt Ltd, |
RCV001218206 | SCV004047531 | likely pathogenic | Alpha-N-acetylgalactosaminidase deficiency type 1 | criteria provided, single submitter | clinical testing | The stop gained c.443G>A (p.Trp148Ter) variant has not been reported in individuals with NAGA-related conditions. The p.Trp148Ter variant has allele frequency of 0.00079% in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. This variant has been reported to the ClinVar database as Pathogenic. The nucleotide change c.443G>A in NAGA is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants have been previously reported to be disease causing. For these reasons, this variant has been classified as Likely Pathogenic. In the absence of another variant, the molecular diagnosis can not be confirmed. |