Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000818668 | SCV000959293 | uncertain significance | Autosomal recessive limb-girdle muscular dystrophy type 2P; Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A9 | 2022-08-22 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 675 of the DAG1 protein (p.Ala675Thr). This variant is present in population databases (rs764063699, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with DAG1-related conditions. ClinVar contains an entry for this variant (Variation ID: 661282). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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 | RCV002535480 | SCV003550008 | uncertain significance | Inborn genetic diseases | 2021-01-27 | criteria provided, single submitter | clinical testing | The c.2023G>A (p.A675T) alteration is located in exon 3 (coding exon 2) of the DAG1 gene. This alteration results from a G to A substitution at nucleotide position 2023, causing the alanine (A) at amino acid position 675 to be replaced by a threonine (T). The p.A675T alteration is predicted to be tolerated by in silico analysis. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |