Submissions for variant NM_006516.4(SLC2A1):c.276-2A>G

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV004552492	SCV004103265	likely pathogenic	SLC2A1-related disorder	2023-03-28	criteria provided, single submitter	clinical testing	The SLC2A1 c.276-2A>G variant is predicted to disrupt the AG splice acceptor site and interfere with normal splicing. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. A different variant at this position (c.276-2A>C) has been reported in a patient with GLUT1 deficiency syndrome 1 (Ramm-Pettersen et al. 2013. PubMed ID: 23448551). Variants that disrupt the consensus splice acceptor site in SLC2A1 are expected to be pathogenic. This variant is interpreted as likely pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003517498	SCV004322385	pathogenic	GLUT1 deficiency syndrome 1, autosomal recessive	2023-09-10	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. Disruption of this splice site has been observed in individual(s) with SLC2A1-related conditions (PMID: 23448551, 26615598; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 3 of the SLC2A1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in SLC2A1 are known to be pathogenic (PMID: 21832227, 26193382).