ClinVar Miner

Submissions for variant NM_033517.1(SHANK3):c.3679dup (p.Ala1227fs) (rs762292772)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000190779 SCV000244220 pathogenic Inborn genetic diseases criteria provided, single submitter clinical testing POSITIVE: Relevant Alteration(s) Detected
GeneDx RCV000366708 SCV000329516 pathogenic not provided 2016-03-23 criteria provided, single submitter clinical testing The c.3679dupG pathogenic variant in the SHANK3 gene has been reported previously in two male siblings with autism, with presumed germline mosaicism in their mother (Durand et al., 2007). The c.3679dupG variant causes a frameshift starting with codon Alanine 1227, changes this amino acid to a Glycine residue, and creates a premature Stop codon at position 69 of the new reading frame, denoted p.Ala1227GlyfsX69. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. As this variant is located in the poly-G tract, no reliable data from control populations were available to accurately assess the frequency of this variant. We interpret c.3679dupG as a pathogenic variant.
Liping Wei Laboratory,Peking University RCV000754675 SCV000804767 pathogenic Autism spectrum disorder 2018-08-01 criteria provided, single submitter research
Ambry Genetics RCV000719974 SCV000850848 pathogenic History of neurodevelopmental disorder 2018-05-08 criteria provided, single submitter clinical testing The c.3679dupG pathogenic mutation, located in coding exon 21 of the SHANK3 gene, results from a duplication of G at nucleotide position 3679, causing a translational frameshift with a predicted alternate stop codon (p.A1227Gfs*69). This has been reported to be a recurrent mutation in patients with autism spectrum disorder and Phelan-McDermid syndrome (Durand CM et al. Nat. Genet., 2007 Jan;39:25-7; De Rubeis S et al. Mol Autism, 2018 Apr;9:31). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Institute for Genomic Statistics and Bioinformatics, University Hospital Bonn RCV000004730 SCV001437685 pathogenic 22q13.3 deletion syndrome criteria provided, single submitter clinical testing PVS1, PS2, PS3, PP5
Laboratoire de Génétique Moléculaire, CHU Bordeaux RCV000366708 SCV001468904 pathogenic not provided criteria provided, single submitter clinical testing
Laboratory of Molecular Genetics (Pr. Bezieau's lab), CHU de Nantes RCV001374986 SCV001572274 pathogenic Neurodevelopmental disorder 2020-09-14 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000366708 SCV001746451 pathogenic not provided 2021-04-01 criteria provided, single submitter clinical testing
OMIM RCV000004730 SCV000024906 pathogenic 22q13.3 deletion syndrome 2007-01-01 no assertion criteria provided literature only
Institute of Human Genetics, Klinikum rechts der Isar RCV000004730 SCV001149930 pathogenic 22q13.3 deletion syndrome 2018-02-07 no assertion criteria provided clinical testing

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