ClinVar Miner

Submissions for variant NM_001082486.2(ACD):c.599C>T (p.Thr200Ile)

gnomAD frequency: 0.00002  dbSNP: rs1181866888
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001064127 SCV001229006 uncertain significance Dyskeratosis congenita, autosomal dominant 6 2022-06-15 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 286 of the ACD protein (p.Thr286Ile). This variant is present in population databases (no rsID available, gnomAD 0.004%). 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. 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: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 858283). This variant has not been reported in the literature in individuals affected with ACD-related conditions.
Johns Hopkins Genomics, Johns Hopkins University RCV001064127 SCV001469037 uncertain significance Dyskeratosis congenita, autosomal dominant 6 2020-12-08 criteria provided, single submitter clinical testing This ACD variant (rs1181866888) is rare (<0.1%) in a large population dataset (gnomAD: 4/251072 total alleles; 0.002%; no homozygotes) and has not been reported in the literature, to our knowledge. This variant has been reported in ClinVar. Two bioinformatic tools queried predict that this substitution would be damaging, and the threonine residue at this position is evolutionarily conserved across most mammals assessed. We consider the clinical significance of c.848C>T to be uncertain at this time.
Ambry Genetics RCV002411583 SCV002676252 uncertain significance Inborn genetic diseases 2023-09-10 criteria provided, single submitter clinical testing The p.T286I variant (also known as c.857C>T), located in coding exon 7 of the ACD gene, results from a C to T substitution at nucleotide position 857. The threonine at codon 286 is replaced by isoleucine, 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.

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