ClinVar Miner

Submissions for variant NM_001321075.3(DLG4):c.1878C>A (p.Cys626Ter)

dbSNP: rs1451196379
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute of Human Genetics, University of Leipzig Medical Center RCV001800214 SCV002044368 pathogenic Intellectual developmental disorder 62 2021-12-21 criteria provided, single submitter research
Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille RCV001800214 SCV002559223 likely pathogenic Intellectual developmental disorder 62 criteria provided, single submitter clinical testing
Tumer Group, Copenhagen University Hospital, Rigshospitalet RCV001800214 SCV003915519 pathogenic Intellectual developmental disorder 62 2023-02-28 criteria provided, single submitter research
Division Of Personalized Genomic Medicine, Columbia University Irving Medical Center RCV001800214 SCV004037363 pathogenic Intellectual developmental disorder 62 2020-06-15 criteria provided, single submitter clinical testing The c.1869C>A (p.Cys623Ter) variant in the DLG4 gene substitutes a cysteine residue to a stop codon at amino acid 623 in the guanylate kinase catalytic domain in coding exon 20 (out of 22 coding exons in total) of the DLG4 gene. This change results in premature protein truncation and is predicted to undergo nonsense mediated mRNA decay (NMD) Analyses of parental samples shows that neither the mother (PGL20-971_C1) nor the father (PGL20-971_C2) harbor this variant. Therefore, the variant appears to be a de novo change. This variant is absent in the Genome Aggregation Database (gnomAD), indicating that it is not a common benign variant in the populations represented therein. Heterozygous loss of function variants in DLG4 have been observed in multiple individuals with clinical features of Intellectual Developmental Disorder 62 (PMIDs: 27479843, 29460436). To the best of our knowledge this exact variant has not been reported in the literature or in ClinVar, however loss of function variants downstream of p.Cys623Ter have been reported to be disease causing.

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