ClinVar Miner

Submissions for variant NM_000359.3(TGM1):c.1420C>T (p.Pro474Ser)

gnomAD frequency: 0.00001  dbSNP: rs1202280089
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Uitto Lab, Thomas Jefferson University RCV000782375 SCV000920896 likely pathogenic Autosomal recessive congenital ichthyosis 1 2018-06-08 criteria provided, single submitter clinical testing
Invitae RCV001377218 SCV001574492 pathogenic not provided 2023-11-06 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 474 of the TGM1 protein (p.Pro474Ser). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individuals with congenital ichthyosis (PMID: 30578701, 31168818, 35412663). ClinVar contains an entry for this variant (Variation ID: 633790). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt TGM1 protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.
Genome-Nilou Lab RCV000782375 SCV002763132 likely pathogenic Autosomal recessive congenital ichthyosis 1 criteria provided, single submitter clinical testing

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