ClinVar Miner

Submissions for variant NM_001082486.2(ACD):c.1268C>T (p.Thr423Met)

gnomAD frequency: 0.00005  dbSNP: rs372747629
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001359630 SCV001555505 uncertain significance Dyskeratosis congenita, autosomal dominant 6 2023-12-19 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 509 of the ACD protein (p.Thr509Met). This variant is present in population databases (rs372747629, gnomAD 0.003%). 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: 1051569). 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.
Ambry Genetics RCV002395795 SCV002708214 uncertain significance Inborn genetic diseases 2023-08-03 criteria provided, single submitter clinical testing The p.T509M variant (also known as c.1526C>T), located in coding exon 11 of the ACD gene, results from a C to T substitution at nucleotide position 1526. The threonine at codon 509 is replaced by methionine, an amino acid with 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.
Fulgent Genetics, Fulgent Genetics RCV001359630 SCV002787427 uncertain significance Dyskeratosis congenita, autosomal dominant 6 2022-01-07 criteria provided, single submitter clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV003321830 SCV004027100 uncertain significance not specified 2024-07-31 criteria provided, single submitter clinical testing

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