ClinVar Miner

Submissions for variant NM_000359.3(TGM1):c.1223_1227del (p.Asp408fs)

gnomAD frequency: 0.00002  dbSNP: rs398122905
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000032735 SCV000386475 likely pathogenic Autosomal recessive congenital ichthyosis 1 2017-04-28 criteria provided, single submitter clinical testing The TGM1 c.1223_1227delACACA (p.Asp408ValfsTer21) variant results in a frameshift and is predicted to result in premature termination of the protein. The p.Asp408ValfsTer21 variant has been reported in four studies in which it is found in a total of eight patients with congenital ichthyosis, including in three in a homozygous state and in five in a compound heterozygous state with the same stop-gained variant on the second allele (Herman et al. 2009; Rodríguez-Pazos et al. 2011; Fachal et al. 2012; Esposito et al. 2013). Facal et al. (2012) report the variant to be present in 21% of disease alleles in the Galician region of Spain. Control data are unavailable for this variant, which is reported at a frequency of 0.00002 in the total population of the Exome Aggregation Consortium. Due to the potential impact of frameshift variants and the supporting evidence from the literature, the p.Asp408ValfsTer21 variant is classified as likely pathogenic for congenital ichthyosis. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
GeneDx RCV000485708 SCV000565615 pathogenic not provided 2022-06-22 criteria provided, single submitter clinical testing Frameshift 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; This variant is associated with the following publications: (PMID: 22511925, 21668430, 19241467, 31589614)
Invitae RCV000485708 SCV000961137 pathogenic not provided 2024-01-29 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Asp408Valfs*21) 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). This variant is present in population databases (rs398122905, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with autosomal recessive congenital ichthyosis (PMID: 19241467, 21668430, 22511925, 23278109). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 39537). For these reasons, this variant has been classified as Pathogenic.
Genome-Nilou Lab RCV000032735 SCV002763429 likely pathogenic Autosomal recessive congenital ichthyosis 1 criteria provided, single submitter clinical testing
Baylor Genetics RCV000032735 SCV004203756 pathogenic Autosomal recessive congenital ichthyosis 1 2024-03-25 criteria provided, single submitter clinical testing
OMIM RCV000032735 SCV000056499 pathogenic Autosomal recessive congenital ichthyosis 1 2011-10-01 no assertion criteria provided literature only
Natera, Inc. RCV000032735 SCV002091217 pathogenic Autosomal recessive congenital ichthyosis 1 2020-11-08 no assertion criteria provided clinical testing

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