ClinVar Miner

Submissions for variant NM_002225.5(IVD):c.464GTG[3] (p.Gly156dup)

dbSNP: rs796051982
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx 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).
Invitae 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, Greenwood Genetic Center RCV000185985 SCV001468010 uncertain significance not provided 2020-10-09 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. 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 2023-06-26 criteria provided, single submitter clinical testing

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