ClinVar Miner

Submissions for variant NM_001082486.2(ACD):c.793C>G (p.Leu265Val)

gnomAD frequency: 0.00005  dbSNP: rs200934242
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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 RCV001051745 SCV001215921 uncertain significance Dyskeratosis congenita, autosomal dominant 6 2023-12-17 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 351 of the ACD protein (p.Leu351Val). This variant is present in population databases (rs200934242, gnomAD 0.1%). 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: 848065). 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.
Genetic Services Laboratory, University of Chicago RCV001819769 SCV002068076 uncertain significance not specified 2020-04-20 criteria provided, single submitter clinical testing DNA sequence analysis of the ACD gene demonstrated a sequence change, c.1051C>G, in exon 9 that results in an amino acid change, p.Leu351Val. This sequence change has been described in the gnomAD database with a low population frequency of 0.012% (dbSNP rs200934242). The p.Leu351Val change affects a moderately conserved amino acid residue located in a domain of the ACD protein that is not known to be functional. The p.Leu351Val substitution appears to be benign using several in-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL). This variant has not been reported in the literature in individuals with ACD-related conditions. Due to the lack of functional studies, the clinical significance of the p.Leu351Val change remains unknown at this time.
Ambry Genetics RCV002400296 SCV002704673 uncertain significance Inborn genetic diseases 2021-07-10 criteria provided, single submitter clinical testing The p.L351V variant (also known as c.1051C>G), located in coding exon 9 of the ACD gene, results from a C to G substitution at nucleotide position 1051. The leucine at codon 351 is replaced by valine, 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.
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV001819769 SCV005090223 uncertain significance not specified 2024-07-31 criteria provided, single submitter clinical testing

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