Submissions for variant NM_004006.3(DMD):c.6179C>T (p.Thr2060Ile)

dbSNP: rs794729000

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000183394	SCV000235847	uncertain significance	not provided	2014-02-26	criteria provided, single submitter	clinical testing	p.Thr2060Ile (ACA>ATA): c.6179 C>T in exon 43 of the DMD gene (NM_004006.2). The T2060I variant in the DMD gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. The T2060I variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. T2060 is a non-conservative amino acid substitution as these residues differ in polarity, charge, size and/or other properties and is more likely to impact secondary structure. However, the T2060 residue is not well conserved across species and in silico analysis predicts T2060I is benign to the protein structure/function. Additionally, missense mutations in nearby residues have not been reported, indicating this region of the protein may tolerate change. With the clinical and molecular information available at this time, we cannot definitively determine if T2060I is a disease-causing mutation or a rare benign variant. The variant is found in CARDIOMYOPATHY panel(s).
Ambry Genetics	RCV002354489	SCV002656835	uncertain significance	Cardiovascular phenotype	2020-08-06	criteria provided, single submitter	clinical testing	The p.T2060I variant (also known as c.6179C>T), located in coding exon 43 of the DMD gene, results from a C to T substitution at nucleotide position 6179. The threonine at codon 2060 is replaced by isoleucine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. 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	RCV002516927	SCV003500518	uncertain significance	Duchenne muscular dystrophy	2024-04-20	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 2060 of the DMD protein (p.Thr2060Ile). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with DMD-related conditions. ClinVar contains an entry for this variant (Variation ID: 201738). 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 not expected to disrupt DMD protein function with a negative predictive value of 95%. 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.
Natera, Inc.	RCV001833101	SCV002091030	uncertain significance	Becker muscular dystrophy; Duchenne muscular dystrophy; Cardiomyopathy; Dystrophin deficiency	2020-05-13	no assertion criteria provided	clinical testing