ClinVar Miner

Submissions for variant NM_000169.3(GLA):c.73G>A (p.Asp25Asn)

gnomAD frequency: 0.00001  dbSNP: rs781788693
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001183525 SCV001349282 uncertain significance Fabry disease 2019-10-04 criteria provided, single submitter clinical testing This missense variant replaces aspartic acid with asparagine at codon 25 of the GLA protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 1/183434 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute RCV001256948 SCV001433477 uncertain significance Hypertrophic cardiomyopathy 1 2019-06-06 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001183525 SCV002054363 uncertain significance Fabry disease 2021-07-15 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV001183525 SCV002779418 uncertain significance Fabry disease 2021-12-24 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001183525 SCV003248410 uncertain significance Fabry disease 2024-09-15 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 25 of the GLA protein (p.Asp25Asn). This variant is present in population databases (rs781788693, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with GLA-related conditions. ClinVar contains an entry for this variant (Variation ID: 923075). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt GLA protein function with a negative predictive value of 95%. 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.
All of Us Research Program, National Institutes of Health RCV001183525 SCV004826188 uncertain significance Fabry disease 2023-05-31 criteria provided, single submitter clinical testing

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