ClinVar Miner

Submissions for variant NM_145331.3(MAP3K7):c.737-7A>G

dbSNP: rs1776199533
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Division of Biology and Genetics, University of Brescia RCV001251209 SCV001371840 pathogenic Cardiospondylocarpofacial syndrome criteria provided, single submitter clinical testing The variant was predicted, in silico, to affect function by the creation of a new splice acceptor site with the retention of the last 6 bases of intron 7 and an in-frame insertion of 2 amino acid residues as a consequence (p.Asn245_Gly246insValVal). RT-PCR on cDNA from patient’s whole blood confirmed this prediction with the insertion of six bases at the RNA level (r.736_737insTTGTAG). Computational analysis revealed that this in-frame insertion alters protein dynamics in the kinase activation loop responsible for TAK1 autophosphorylation after binding with its interactor TAB1.
GeneDx RCV001655703 SCV001871058 pathogenic not provided 2023-09-14 criteria provided, single submitter clinical testing Published RNA studies on patient blood indicated creation of a new cryptic splice acceptor site resulting in the insertion of six bases at the RNA level (r.736_737insTTGTAG), and in-frame insertion of two amino acids at the protein level (p.Asn245_Gly246insValVal) (Morlino et al., 2018); Not observed in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 29467388, 32105826)
OMIM RCV001251209 SCV002073671 pathogenic Cardiospondylocarpofacial syndrome 2022-02-04 no assertion criteria provided literature only

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