Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000439035 | SCV000533677 | likely pathogenic | not provided | 2016-11-08 | criteria provided, single submitter | clinical testing | The G110E missense variant in the GALT gene has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The G110E variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The G110E variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved in mammals, and the majority of in silico analysis models predict that this variant is probably damaging to the protein structure/function. Furthermore, missense variants in nearby residues (S112R, D113N, H114L) have been reported in the Human Gene Mutation Database in association with classic galactosemia (Stenson et al., 2014), supporting the functional importance of this region of the protein. In summary, we interpret the G110E variant as likely pathogenic; however, the possibility that it is benign cannot be excluded. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000439035 | SCV000695689 | uncertain significance | not provided | 2016-08-02 | criteria provided, single submitter | clinical testing | Variant summary: The GALT c.329G>A (p.Gly110Glu) variant involves the alteration of a conserved nucleotide. 2/4 in silico tools predict a benign outcome (SNPs&GO not captured due to low reliability index). The variant is located in the last nucleotide position in exon 4. 5/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant is absent in 121370 control chromosomes. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant was classified as a variant of uncertain significance (VUS) until additional information becomes available. |