Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000055919 | SCV000762536 | pathogenic | Creatine transporter deficiency | 2022-04-06 | criteria provided, single submitter | clinical testing | This missense change has been observed in individuals with creatine transporter deficiency and X-linked mental retardation due to SLC6A8-deficiency (PMID: 15154114, 21836662, 23660394, 25803912). It has also been observed to segregate with disease in related individuals. This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 554 of the SLC6A8 protein (p.Pro554Leu). This variant is not present in population databases (gnomAD no frequency). ClinVar contains an entry for this variant (Variation ID: 65693). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SLC6A8 protein function. Experimental studies have shown that this missense change affects SLC6A8 function (PMID: 17465020). For these reasons, this variant has been classified as Pathogenic. |
Institute Of Human Genetics Munich, |
RCV000055919 | SCV001150258 | pathogenic | Creatine transporter deficiency | 2019-06-07 | criteria provided, single submitter | clinical testing |