Submissions for variant NM_001082486.2(ACD):c.791C>T (p.Thr264Ile)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV002400895	SCV002706473	uncertain significance	Inborn genetic diseases	2021-07-18	criteria provided, single submitter	clinical testing	The p.T350I variant (also known as c.1049C>T), located in coding exon 9 of the ACD gene, results from a C to T substitution at nucleotide position 1049. The threonine at codon 350 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003100748	SCV003005468	uncertain significance	Dyskeratosis congenita, autosomal dominant 6	2022-09-14	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 expected to disrupt ACD protein function. This variant has not been reported in the literature in individuals affected with ACD-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 350 of the ACD protein (p.Thr350Ile).