ClinVar Miner

Submissions for variant NM_001082486.2(ACD):c.1226G>A (p.Arg409His)

gnomAD frequency: 0.00005  dbSNP: rs374742891
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001220729 SCV001392738 uncertain significance Dyskeratosis congenita, autosomal dominant 6 2023-03-10 criteria provided, single submitter clinical testing 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ACD protein function. ClinVar contains an entry for this variant (Variation ID: 949293). This variant has not been reported in the literature in individuals affected with ACD-related conditions. This variant is present in population databases (rs374742891, gnomAD 0.03%). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 495 of the ACD protein (p.Arg495His).
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV002268455 SCV002551704 uncertain significance not specified 2024-07-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV002393529 SCV002701613 uncertain significance Inborn genetic diseases 2023-09-17 criteria provided, single submitter clinical testing The p.R495H variant (also known as c.1484G>A), located in coding exon 11 of the ACD gene, results from a G to A substitution at nucleotide position 1484. The arginine at codon 495 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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