ClinVar Miner

Submissions for variant NM_000359.3(TGM1):c.401A>G (p.Tyr134Cys)

gnomAD frequency: 0.00001  dbSNP: rs147916609
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000666280 SCV000790544 likely pathogenic Autosomal recessive congenital ichthyosis 1 2017-03-28 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001215792 SCV001387554 pathogenic not provided 2024-01-11 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 134 of the TGM1 protein (p.Tyr134Cys). This variant is present in population databases (rs147916609, gnomAD 0.003%). This missense change has been observed in individuals with TGM1-related conditions (PMID: 18948357, 19241467, 26762237, 27025581). ClinVar contains an entry for this variant (Variation ID: 551268). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on TGM1 protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. This variant disrupts the p.Tyr134 amino acid residue in TGM1. Other variant(s) that disrupt this residue have been observed in individuals with TGM1-related conditions (PMID: 30578701), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV001215792 SCV001820209 pathogenic not provided 2024-03-28 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (gnomAD); In silico analysis supports a deleterious effect on splicing; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 27025581, 22992804, 31168818, 30916489, 26762237, 19241467, 18948357)
Genome-Nilou Lab RCV000666280 SCV002764028 likely pathogenic Autosomal recessive congenital ichthyosis 1 criteria provided, single submitter clinical testing
Baylor Genetics RCV000666280 SCV004203765 pathogenic Autosomal recessive congenital ichthyosis 1 2024-03-30 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000666280 SCV005629778 likely pathogenic Autosomal recessive congenital ichthyosis 1 2024-03-06 criteria provided, single submitter clinical testing

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