ClinVar Miner

Submissions for variant NM_005710.2(PQBP1):c.451_452AG[4] (p.Arg153fs) (rs606231193)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000623728 SCV000741124 pathogenic Inborn genetic diseases 2014-06-06 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: POSITIVE: Relevant Alteration(s) Detected
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV000414864 SCV000492595 pathogenic Hyperactivity; Delayed speech and language development; Microcephaly 2016-05-16 no assertion criteria provided clinical testing
GeneDx RCV000254782 SCV000322220 pathogenic not provided 2018-09-26 criteria provided, single submitter clinical testing The c.459_462delAGAG pathogenic variant in the PQBP1 gene has been reported previously in association with Renpenning syndrome and other forms of X-linked intellectual disability (Kalscheuer et al., 2003; Sheen et al., 2010; Germanaud et al., 2011). Functional studies show c.459_462delAGAG transcripts were markedly reduced compared to the control, which indicated nonsense mediated mRNA decay (Kalscheuer et al., 2003). Other studies show c.459_462delAGAG causes loss of the YxxPxxVL motif that is essential for binding with the spliceosomal protein U5–15kD (Mizuguchi et al., 2014). The c.459_462delAGAG variant causes a frameshift starting with codon Arginine 153, changes this amino acid to a Serine residue, and creates a premature Stop codon at position 41 of the new reading frame, denoted p.Arg153SerfsX41. This frameshift variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.459_462delAGAG variant is not observed in large population cohorts (Lek et al., 2016). Therefore, the presence of c.459_462delAGAG is consistent with the diagnosis of a PQBP1-related disorder in this individual.
Laboratoire de Cytogenetique,Hospices Civils de Lyon RCV000011727 SCV000890116 pathogenic Renpenning syndrome 1 2017-07-11 criteria provided, single submitter clinical testing
Molecular Genetics Laboratory,BC Children's and BC Women's Hospitals RCV000011727 SCV000599277 pathogenic Renpenning syndrome 1 2016-06-14 criteria provided, single submitter clinical testing
OMIM RCV000011727 SCV000031959 pathogenic Renpenning syndrome 1 2005-05-01 no assertion criteria provided literature only
Raymond Lab,University of Cambridge RCV000850214 SCV000897752 likely pathogenic Intellectual disability 2019-02-13 criteria provided, single submitter research

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