ClinVar Miner

Submissions for variant NM_001375524.1(TRRAP):c.8702G>C (p.Cys2901Ser)

gnomAD frequency: 0.00001  dbSNP: rs141693208
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002894929 SCV003245017 uncertain significance not provided 2022-07-11 criteria provided, single submitter clinical testing In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This sequence change replaces cysteine, which is neutral and slightly polar, with serine, which is neutral and polar, at codon 2876 of the TRRAP protein (p.Cys2876Ser). This variant is present in population databases (rs141693208, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with TRRAP-related conditions. 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0").
Revvity Omics, Revvity RCV002894929 SCV003821574 uncertain significance not provided 2021-04-08 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003331395 SCV004038502 uncertain significance not specified 2023-08-09 criteria provided, single submitter clinical testing Variant summary: TRRAP c.8627G>C (p.Cys2876Ser) results in a non-conservative amino acid change located in the PIK-related kinase, FAT (IPR003151) of the encoded protein sequence. Two of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 1.3e-05 in 231238 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.8627G>C in individuals affected with Developmental Delay With Or Without Dysmorphic Facies And Autism and no experimental evidence demonstrating its impact on protein function have been reported. Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Both submitters classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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