Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001213939 | SCV001385600 | uncertain significance | Congenital myasthenic syndrome 12 | 2019-10-29 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with GFPT1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with serine at codon 39 of the GFPT1 protein (p.Gly39Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. This variant also falls at the last nucleotide of exon 2 of the GFPT1 coding sequence, which is part of the consensus splice site for this exon. |