Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001044886 | SCV001208707 | uncertain significance | Charcot-Marie-Tooth disease type 4A | 2020-11-24 | 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. 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 GDAP1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces asparagine with histidine at codon 298 of the GDAP1 protein (p.Asn298His). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and histidine. |
| Ambry Genetics | RCV002445244 | SCV002682040 | uncertain significance | Inborn genetic diseases | 2021-05-05 | criteria provided, single submitter | clinical testing | The p.N298H variant (also known as c.892A>C), located in coding exon 6 of the GDAP1 gene, results from an A to C substitution at nucleotide position 892. The asparagine at codon 298 is replaced by histidine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |