ClinVar Miner

Submissions for variant NM_001082486.2(ACD):c.266G>T (p.Arg89Leu)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002340945 SCV002645401 uncertain significance Inborn genetic diseases 2021-10-27 criteria provided, single submitter clinical testing The p.R175L variant (also known as c.524G>T), located in coding exon 3 of the ACD gene, results from a G to T substitution at nucleotide position 524. The arginine at codon 175 is replaced by leucine, an amino acid with dissimilar 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.
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV003493939 SCV004242715 uncertain significance not specified 2024-02-06 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003776073 SCV004677425 uncertain significance Dyskeratosis congenita, autosomal dominant 6 2024-01-09 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 175 of the ACD protein (p.Arg175Leu). This variant is present in population databases (rs762580062, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with ACD-related conditions. ClinVar contains an entry for this variant (Variation ID: 1746352). 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 expected to disrupt ACD protein function with a positive predictive value of 80%. 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.

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