ClinVar Miner

Submissions for variant NM_000169.3(GLA):c.313A>G (p.Arg105Gly)

gnomAD frequency: 0.00001  dbSNP: rs782092398
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001059595 SCV001224222 uncertain significance Fabry disease 2022-08-18 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 105 of the GLA protein (p.Arg105Gly). This variant is present in population databases (rs782092398, gnomAD 0.008%). 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: 854523). 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: "Benign"; Align-GVGD: "Class C45"). 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 RCV002320312 SCV002610606 uncertain significance Cardiovascular phenotype 2023-02-16 criteria provided, single submitter clinical testing The p.R105G variant (also known as c.313A>G), located in coding exon 2 of the GLA gene, results from an A to G substitution at nucleotide position 313. The arginine at codon 105 is replaced by glycine, an amino acid with dissimilar properties. This alteration has been reported in individuals with symptoms consistent with Fabry disease (Ambry internal data), as well as in a newborn screening cohort with enzymatic deficiency noted (Sanders KA et al. Int J Neonatal Screen, 2020 Jun;6:). Based on internal structural analysis, this alteration was potentially disruptive to the structure of the GLA protein (Ambry internal data). Based on data from gnomAD, the G allele has an overall frequency of 0.0005450% (1/183486) total alleles studied, with 0 hemizygote(s) observed. The highest observed frequency was 0.007598% (1/13161) of African alleles. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001059595 SCV002081352 uncertain significance Fabry disease 2021-09-03 no assertion criteria provided clinical testing

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