ClinVar Miner

Submissions for variant NM_000159.4(GCDH):c.416C>T (p.Ser139Leu) (rs139851890)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169288 SCV000220604 likely pathogenic Glutaric aciduria, type 1 2014-08-20 criteria provided, single submitter literature only
GeneDx RCV000254928 SCV000321705 pathogenic not provided 2015-04-14 criteria provided, single submitter clinical testing The S139L missense variant has been reported previously in association with glutaric aciduria type I (GA1) (Goodman et al., 1998). This variant is associated with 0.2% of normal glutaryl-CoA dehydrogenase activity when expressed in E. coli (Goodman et al., 1998).
Department of Genetics,Sultan Qaboos University Hospital, Oman RCV000169288 SCV000891511 uncertain significance Glutaric aciduria, type 1 2017-12-30 criteria provided, single submitter curation
Fulgent Genetics,Fulgent Genetics RCV000169288 SCV000894185 pathogenic Glutaric aciduria, type 1 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV000169288 SCV001235363 pathogenic Glutaric aciduria, type 1 2019-12-04 criteria provided, single submitter clinical testing This sequence change replaces serine with leucine at codon 139 of the GCDH protein (p.Ser139Leu). The serine residue is highly conserved and there is a large physicochemical difference between serine and leucine. This variant is present in population databases (rs139851890, ExAC 0.01%). This variant has been observed to be homozygous or in combination with another GCDH variant in individuals affected with glutaric aciduria type I (PMID: 16377226, 20514322, 21176883, 26656312, 28143689). ClinVar contains an entry for this variant (Variation ID: 188921). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. For these reasons, this variant has been classified as Pathogenic.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000254928 SCV001247982 pathogenic not provided 2019-09-01 criteria provided, single submitter clinical testing

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