Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000185985 | SCV000238944 | likely pathogenic | not provided | 2014-02-07 | criteria provided, single submitter | clinical testing | A c.476_478dupGTG sequence change that is likely pathogenic was identified in the IVD gene. The normal sequence with the inserted bases in brackets is AGTG{GTG}AGTA. It has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The insertion of three nucleotides causes a insertion of a Glycine at amino acid position 159, denoted p.Gly159ins. The Glycine at position 159 is a highly conserved residue in the IVD protein that is located within a moderately conserved region of the protein. A missense mutation at this position (G159A) has been reported in association with isovaleric acidemia. Therefore, c.476_478dupGTG is a strong candidate for a disease-causing mutation, however the possibility that it is a benign variant cannot be excluded. The variant is found in IVD panel(s). |
Labcorp Genetics |
RCV001040480 | SCV001204056 | uncertain significance | Isovaleryl-CoA dehydrogenase deficiency | 2023-12-30 | criteria provided, single submitter | clinical testing | This variant, c.476_478dup, results in the insertion of 1 amino acid(s) of the IVD protein (p.Gly159dup), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs796051982, gnomAD 0.009%). This variant has been observed in individual(s) with isovaleric acidemia (PMID: 31707166). This variant is also known as c.472_473insGTG (p.Ser158_Gly159insGly). ClinVar contains an entry for this variant (Variation ID: 203791). 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. |
Greenwood Genetic Center Diagnostic Laboratories, |
RCV000185985 | SCV001468010 | uncertain significance | not provided | 2020-10-09 | criteria provided, single submitter | clinical testing | |
Myriad Genetics, |
RCV001040480 | SCV002060118 | uncertain significance | Isovaleryl-CoA dehydrogenase deficiency | 2021-11-03 | criteria provided, single submitter | clinical testing | NM_002225.3(IVD):c.476_478dupGTG(G159dup) is an in-frame duplication classified as a variant of uncertain significance in the context of isovaleric acidemia. G159dup has been observed in cases with relevant disease (PMID: 31707166). Functional assessments of this variant are not available in the literature. G159dup has been observed in population frequency databases (gnomAD: AMR 0.01%). In summary, there is insufficient evidence to classify NM_002225.3(IVD):c.476_478dupGTG(G159dup) as pathogenic or benign. Please note: this variant was assessed in the context of healthy population screening. |
Ambry Genetics | RCV002517825 | SCV003701640 | uncertain significance | Inborn genetic diseases | 2022-04-13 | criteria provided, single submitter | clinical testing | The c.476_478dupGTG (p.G159dup) alteration is located in exon 5 (coding exon 5) of the IVD gene. The alteration consists of an in-frame duplication of 3 nucleotides from position 476 to 478, resulting in the duplication of 1 residue. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Baylor Genetics | RCV001040480 | SCV004198027 | likely pathogenic | Isovaleryl-CoA dehydrogenase deficiency | 2023-11-22 | criteria provided, single submitter | clinical testing |