Submissions for variant NM_001918.5(DBT):c.292A>G (p.Ile98Val)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003077075	SCV003455433	uncertain significance	Maple syrup urine disease	2022-04-08	criteria provided, single submitter	clinical testing	This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 98 of the DBT protein (p.Ile98Val). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with DBT-related conditions. 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 DBT protein function. 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	RCV004070426	SCV004852747	uncertain significance	Inborn genetic diseases	2024-01-09	criteria provided, single submitter	clinical testing	The c.292A>G (p.I98V) alteration is located in exon 4 (coding exon 4) of the DBT gene. This alteration results from a A to G substitution at nucleotide position 292, causing the isoleucine (I) at amino acid position 98 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.