ClinVar Miner

Submissions for variant NM_000359.3(TGM1):c.1645+1G>T

gnomAD frequency: 0.00001  dbSNP: rs774242987
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV002016938 SCV002307375 likely pathogenic not provided 2021-01-11 criteria provided, single submitter clinical testing In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with TGM1-related conditions. This variant is present in population databases (rs774242987, ExAC 0.006%). This sequence change affects a donor splice site in intron 11 of the TGM1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in TGM1 are known to be pathogenic (PMID: 18948357, 19241467).
Institute for Human Genetics and Genomic Medicine, Uniklinik RWTH Aachen RCV002267141 SCV002549127 pathogenic Autosomal recessive congenital ichthyosis 1 2022-06-23 criteria provided, single submitter clinical testing The detected change is reported in the dbSNP database (dbSNP151 as of 06/23/2022) with the designation rs774242987. In gnomAD it is listed with a frequency of 0.001061% (3/282686) (as of 06/23/2022). The change affects the canonical splice site and in all likelihood leads to altered splicing and usually to loss of function of the corresponding protein. The variant is currently to be regarded as a "pathogenic variant" (ACMG criteria).
Genome-Nilou Lab RCV002267141 SCV002763021 likely pathogenic Autosomal recessive congenital ichthyosis 1 criteria provided, single submitter clinical testing
Baylor Genetics RCV002267141 SCV004203824 likely pathogenic Autosomal recessive congenital ichthyosis 1 2022-08-02 criteria provided, single submitter clinical testing

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