Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000187562 | SCV000241156 | uncertain significance | not provided | 2014-12-19 | criteria provided, single submitter | clinical testing | p.Gln97His (CAG>CAT): c.291 G>T in exon 2 of the GAMT gene (NM_000156.4) The Q97H variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,500 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 Q97H variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. In silico analysis predicts this variant is probably damaging to the protein structure/function. However, this substitution occurs at a position that is not conserved across species. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in CHILD-EPI panel(s). |
Labcorp Genetics |
RCV002517860 | SCV003301935 | uncertain significance | Cerebral creatine deficiency syndrome | 2022-02-21 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 97 of the GAMT protein (p.Gln97His). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with GAMT-related conditions. ClinVar contains an entry for this variant (Variation ID: 205578). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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 | RCV004020268 | SCV004873732 | uncertain significance | Inborn genetic diseases | 2024-03-04 | criteria provided, single submitter | clinical testing | The c.291G>T (p.Q97H) alteration is located in exon 2 (coding exon 2) of the GAMT gene. This alteration results from a G to T substitution at nucleotide position 291, causing the glutamine (Q) at amino acid position 97 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Natera, |
RCV001827998 | SCV002087045 | uncertain significance | Deficiency of guanidinoacetate methyltransferase | 2019-10-28 | no assertion criteria provided | clinical testing |