Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV000867843 | SCV002600175 | likely benign | Creatine transporter deficiency | 2022-06-06 | reviewed by expert panel | curation | The NM_005629.4:c.354C>T (p.Ala118=) variant in SLC6A8 is a synonymous (silent) variant that is not predicted by SpliceAI or varSEAK to impact splicing, and it occurs at a nucleotide that is not conserved (BP4, BP7). The variant is absent in gnomAD v2.1.1 (PM2_Supporting). To our knowledge, this variant has not been reported in any patients with creatine transporter deficiency in the literature. There is a ClinVar entry for this variant (Variation ID: 511340). Although this variant is rare (meeting PM2_Supporting), it has been classified as likely benign by the ClinGen Creatine Deficiency Syndromes (CCDS) Variant Curation Expert Panel (VCEP) based on the recommendation of Richards et al (PMID: 25741868) because it is a synonymous variant, the altered nucleotide is not highly conserved, computational prediction suggests no impact on splicing, and there is no additional evidence to suggest that the variant is disease-causing. SLC6A8-specific ACMG/AMP criteria applied, as specified by the ClinGen LSD VCEP (specifications version 1.1.0): PM2_Supporting, BP4, BP7. (Classification approved by the ClinGen CCDS VCEP on June 6, 2022). |
Gene |
RCV000605861 | SCV000721877 | likely benign | not specified | 2017-08-10 | criteria provided, single submitter | clinical testing | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. |
Invitae | RCV000867843 | SCV001009112 | likely benign | Creatine transporter deficiency | 2023-08-25 | criteria provided, single submitter | clinical testing |