ClinVar Miner

Submissions for variant NM_000359.3(TGM1):c.1042C>T (p.Arg348Ter)

gnomAD frequency: 0.00001  dbSNP: rs1296165092
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000672174 SCV000797253 pathogenic Autosomal recessive congenital ichthyosis 1 2018-01-18 criteria provided, single submitter clinical testing
GeneDx RCV001592854 SCV001814256 pathogenic not provided 2020-04-06 criteria provided, single submitter clinical testing Observed with another TGM1 variant on the opposite allele (in trans) in a patient with lamellar ichthyosis from the published literature (Kon et al., 2003); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 12535215, 25525159)
Labcorp Genetics (formerly Invitae), Labcorp RCV001592854 SCV002239134 pathogenic not provided 2022-04-08 criteria provided, single submitter clinical testing This variant is present in population databases (no rsID available, gnomAD 0.0008%). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 556205). This premature translational stop signal has been observed in individual(s) with congenital ichthyosis (PMID: 12535215). This sequence change creates a premature translational stop signal (p.Arg348*) in the TGM1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TGM1 are known to be pathogenic (PMID: 18948357, 19241467).
CeGaT Center for Human Genetics Tuebingen RCV001592854 SCV002497705 pathogenic not provided 2022-07-01 criteria provided, single submitter clinical testing TGM1: PVS1, PM2, PM3
Genome-Nilou Lab RCV000672174 SCV002763718 pathogenic Autosomal recessive congenital ichthyosis 1 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003387906 SCV004099633 pathogenic Lamellar ichthyosis 2023-09-08 criteria provided, single submitter clinical testing Variant summary: TGM1 c.1042C>T (p.Arg348X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 4e-06 in 250840 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1042C>T has been reported in the literature in individuals affected with Lamellar Ichthyosis (e.g., Youssefian_2019). These data indicate that the variant is very likely to be associated with disease. The following publication was ascertained in the context of this evaluation (PMID: 30578701). Four submitters have reported clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Baylor Genetics RCV000672174 SCV005054266 pathogenic Autosomal recessive congenital ichthyosis 1 2024-02-14 criteria provided, single submitter clinical testing

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