Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Victorian Clinical Genetics Services, |
RCV004595246 | SCV005086067 | likely pathogenic | Creatine transporter deficiency | 2024-10-09 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Likely 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 1 (MIM#300352). (I) 0109 - This gene is associated with X-linked disease. Heterozygous females are typically either asymptomatic or have mild intellectual disability (PMIDs: 11898126, 11326334, 20301745). No correlation has been found between skewed X-chromosome inactivation in favour of the pathogenic variant and severity of clinical phenotype (PMID: 20301745). (I) 0200 - Variant is predicted to result in a missense amino acid change from glycine to aspartic acid. (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (SP) 0603 - Missense variant in a region that is highly intolerant to missense variation (high constraint region in DECIPHER). (SP) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0807 - This variant has no previous evidence of pathogenicity. (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1204 - This variant has been inferred to be de novo in the proband (by duo analysis with the mother and segregation testing of half-sister). (SP) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |