Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001381037 | SCV001579289 | pathogenic | Cerebral creatine deficiency syndrome | 2023-09-21 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1069228). This variant has not been reported in the literature in individuals affected with GAMT-related conditions. This sequence change creates a premature translational stop signal (p.Trp20*) in the GAMT gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GAMT are known to be pathogenic (PMID: 15108290). |
| Baylor Genetics | RCV003462972 | SCV004198572 | likely pathogenic | Deficiency of guanidinoacetate methyltransferase | 2023-10-03 | criteria provided, single submitter | clinical testing | |
| Neuberg Centre For Genomic Medicine, |
RCV003462972 | SCV005438753 | likely pathogenic | Deficiency of guanidinoacetate methyltransferase | 2023-07-22 | criteria provided, single submitter | clinical testing | The observed stop gained c.59G>Ap.Trp20Ter variant has been submitted to the ClinVar database as Pathogenic. This variant has not been identified in affected individuals in the literature, to our knowledge. The c.59G>A variant is absent in gnomAD Exomes. The nucleotide change c.59G>A in GAMT is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. This sequence change creates a premature translational stop signal p.Trp20Ter in the GAMT gene. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants in GAMT gene have been previously reported to be disease causing Item CB, et al., 2004. A prevalent missense pathogenic variant c.59G>C | p.Trp20Ser in GAMT gene at the same position has been reported previously in multiple affected individuals, suggesting that this residue might be of clinical significance Almeida LS, et al., 2007. However, additional functional studies will be required to prove the pathogenicity of p.Trp20Ter variant. For these reasons, this variant has been classified as Likely Pathogenic. |
| Fulgent Genetics, |
RCV003462972 | SCV005655125 | likely pathogenic | Deficiency of guanidinoacetate methyltransferase | 2024-02-02 | criteria provided, single submitter | clinical testing |