Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001383246 | SCV001582334 | pathogenic | Cerebral creatine deficiency syndrome | 2022-11-15 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 1070918). This variant has not been reported in the literature in individuals affected with GAMT-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Asp119Glufs*8) 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 | RCV003462990 | SCV004198592 | likely pathogenic | Deficiency of guanidinoacetate methyltransferase | 2023-06-13 | criteria provided, single submitter | clinical testing | |
Victorian Clinical Genetics Services, |
RCV003462990 | SCV005086521 | pathogenic | Deficiency of guanidinoacetate methyltransferase | 2023-07-17 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with cerebral creatine deficiency syndrome 2 (MIM#612736). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0701 - Other NMD-predicted variants comparable to the one identified in this case have very strong previous evidence for pathogenicity. These variants have been reported many times as pathogenic (DECIPHER). (SP) 0803 - This variant has limited previous evidence of pathogenicity in an unrelated individual. This variant has been reported once as pathogenic (ClinVar). (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1206 - This variant has been shown to be paternally inherited (by trio analysis). (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |
Fulgent Genetics, |
RCV003462990 | SCV005655114 | likely pathogenic | Deficiency of guanidinoacetate methyltransferase | 2024-03-24 | criteria provided, single submitter | clinical testing |