ClinVar Miner

Submissions for variant NM_001375524.1(TRRAP):c.3104G>A (p.Arg1035Gln)

dbSNP: rs2116495143
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
3billion, Medical Genetics RCV001775301 SCV002012063 pathogenic Developmental delay with or without dysmorphic facies and autism 2021-10-02 criteria provided, single submitter clinical testing The variant is not observed in the gnomAD v2.1.1 dataset (PM2). Functional studies provide strong evidence of the variant having a damaging effect on the gene or gene product (PMID: 30827496). A different missense change at the same codon (p.Arg1035Gly) has been reported as pathogenic (VCV000977633.1, PM5). The variant was observed as assumed (i.e. paternity and maternity not confirmed) de novoo (3billion dataset, PM6). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.
Institute of Human Genetics, University of Leipzig Medical Center RCV001775301 SCV002044455 pathogenic Developmental delay with or without dysmorphic facies and autism 2021-12-17 criteria provided, single submitter clinical testing This variant was identified as de novo (maternity and paternity confirmed)._x000D_ Criteria applied: PS2, PS4_MOD, PM2_SUP, PM5_SUP, PP2, PP3
GeneDx RCV002272495 SCV002558647 pathogenic not provided 2022-01-25 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 30827496)
Labcorp Genetics (formerly Invitae), Labcorp RCV002272495 SCV003482759 pathogenic not provided 2022-04-15 criteria provided, single submitter clinical testing Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 1320128). This missense change has been observed in individual(s) with TRRAP-related intellectual disability (PMID: 30827496; Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1035 of the TRRAP protein (p.Arg1035Gln). For these reasons, this variant has been classified as Pathogenic.
Juno Genomics, Hangzhou Juno Genomics, Inc RCV001775301 SCV005417931 likely pathogenic Developmental delay with or without dysmorphic facies and autism criteria provided, single submitter clinical testing PM2_Supporting+PP2+PS4_Supporting+PM6+PP4

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