ClinVar Miner

Submissions for variant NM_002225.5(IVD):c.148C>T (p.Arg50Cys) (rs34695403)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000003748 SCV000941046 likely pathogenic Isovaleryl-CoA dehydrogenase deficiency 2018-12-24 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 53 of the IVD protein (p.Arg53Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs34695403, ExAC 0.009%). This variant has been observed in individuals affected with isovaleric acidemia (PMID: 10677295, Invitae). ClinVar contains an entry for this variant (Variation ID: 3567). This variant is also know as p.Arg21Cys in the literature. This variant has been reported to affect RNA splicing of the IVD gene (PMID:10677295). This variant disrupts the p.Arg53 amino acid residue in IVD. Other variant(s) that disrupt this residue have been observed in individuals with IVD-related conditions (PMID: 17576084, 15486829, 10677295, 19099814, 17027310, 27904153), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Baylor Genetics RCV000003748 SCV001163379 likely pathogenic Isovaleryl-CoA dehydrogenase deficiency criteria provided, single submitter clinical testing
OMIM RCV000003748 SCV000023913 pathogenic Isovaleryl-CoA dehydrogenase deficiency 2000-02-01 no assertion criteria provided literature only
Natera, Inc. RCV000003748 SCV001460257 likely pathogenic Isovaleryl-CoA dehydrogenase deficiency 2020-09-16 no assertion criteria provided clinical testing

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