Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000707528 | SCV000836629 | uncertain significance | Alacrima, achalasia, and intellectual disability syndrome | 2018-04-11 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine with isoleucine at codon 36 of the GMPPA protein (p.Met36Ile). The methionine residue is highly conserved and there is a small physicochemical difference between methionine and isoleucine. This variant is present in population databases (rs745438072, ExAC 0.02%). This variant has not been reported in the literature in individuals with GMPPA-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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. |
| Ambry Genetics | RCV003165934 | SCV003877901 | uncertain significance | Inborn genetic diseases | 2023-02-23 | criteria provided, single submitter | clinical testing | The c.108G>C (p.M36I) alteration is located in exon 3 (coding exon 2) of the GMPPA gene. This alteration results from a G to C substitution at nucleotide position 108, causing the methionine (M) at amino acid position 36 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |