Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Clin |
RCV000640934 | SCV002600193 | likely pathogenic | Creatine transporter deficiency | 2022-06-06 | reviewed by expert panel | curation | The NM_005629.4(SLC6A8):c.53_137delinsCCGTGT (p.Lys18fs) variant in SLC6A8 is a frameshift variant predicted to cause a premature stop codon in biologically-relevant-exon 1/13, leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1). This variant is absent in population databases (PM2_Supporting), and to our current knowledge has not been reported in affected individuals in the literature. There is a ClinVar entry for this variant (Variation ID:533702). In summary, this variant meets the criteria to be classified as Likely Pathogenic for Creatine Transporter Deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen Cerebral Creatine Deficiency Syndromes Variant Curation Expert Panel (Specifications Version 1.0): PVS1, PM2_Supporting. (Classification approved by the ClinGen CCDS VCEP on June 6, 2022). |
| Labcorp Genetics |
RCV000640934 | SCV000762539 | pathogenic | Creatine transporter deficiency | 2018-12-26 | criteria provided, single submitter | clinical testing | Loss-of-function variants in SLC6A8 are known to be pathogenic (PMID: 22281021). For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals with SLC6A8-related disease. This sequence change creates a premature translational stop signal (p.Lys18Thrfs*53) in the SLC6A8 gene. It is expected to result in an absent or disrupted protein product. While this variant is not present in population databases, the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. |