Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV003334341 | SCV004042599 | uncertain significance | Creatine transporter deficiency | 2023-03-23 | reviewed by expert panel | curation | The NM_005629.4(SLC6A8):c.407C>T variant in SLC6A8 is a missense variant predicted to cause substitution of Alanine for Valine at amino acid 136 p.(Ala136Val). This variant is absent from gnomAD v2.1.1, therefore PM2_Supporting criteria is applicable. The computational predictor REVEL gives a score of 0.873 which is above the threshold of 0.75 established for in silico predictions, therefore PP3 criteria is applicable. This variant has not been previously reported in ClinVar, and a different amino acid change at the same amino acid is reported there as a Variant of Uncertain Significance (c.406G>A (p.Ala136Thr); VarID:1285463). At the time of this curation, this variant has not been reported in individuals with suspected Creatine Transporter Deficiency in the literature. In summary, this variant meets the criteria to be classified as a Variant of Uncertain Significance 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): PM2_Supporting, PP3. (Classification approved by the ClinGen CCDS VCEP, March 23, 2023) |