ClinVar Miner

Submissions for variant NM_005629.4(SLC6A8):c.318_320CTT[1] (p.Phe107del) (rs80338739)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000479265 SCV000568381 pathogenic not provided 2016-12-29 criteria provided, single submitter clinical testing The c.321_323delCTT variant in the SLC6A8 gene has previously been reported in two related males with severe language delay, intellectual disability, poor motor development, microcephaly, absent creatine signaling on brain MRS, elevated urinary creatine/creatinine ratio, and impaired creatine uptake in cultured fibroblasts; symptomatic and asymptomatic females were also reported in that family (Salomons et al., 2003; DeGrauw et al., 2002). A whole exome trio study by Zhu et al. (2015) identified the c.321_323delCTT variant in a male with athetoid cerebral palsy, developmental delay, seizures, and recurrent vomiting. The c.321_323delCTT variant causes an in-frame deletion of one amino acid, Phenylalanine 107, denoted p.Phe107del. This amino acid deletion occurs at a position that is conserved across species. A functional study demonstrated expression of the c.321_323delCTT variant transiently transfected in SLC6A8-deficient fibroblasts did not restore creatine uptake (Rosenberg et al., 2007). The c.321_323delCTT variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret c.321_323delCTT as a pathogenic variant.
Ambry Genetics RCV000623073 SCV000742827 likely pathogenic Inborn genetic diseases 2017-07-31 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: LIKELY POSITIVE: Relevant Alteration(s) Detected
GeneReviews RCV000020635 SCV000041155 pathologic Creatine transporter deficiency 2011-08-18 no assertion criteria provided curation Converted during submission to Pathogenic.
GenomeConnect-Association for Creatine Deficiencies RCV000020635 SCV001169655 not provided Creatine transporter deficiency no assertion provided phenotyping only Variant interpreted as Likely pathogenic and reported on 08-25-2017 by GTR ID 61756. Assertions are reported exactly as they appear on the patient provided laboratory report. GenomeConnect facilitates ClinVar submission from the Association for Creatine Deficiencies registry and does not attempt to reinterpret the variant.

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