ClinVar Miner

Submissions for variant NM_201631.4(TGM5):c.122T>C (p.Leu41Pro) (rs143601447)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000442177 SCV000520931 likely pathogenic not provided 2016-10-06 criteria provided, single submitter clinical testing The L41P variant in the TGM5 gene has been reported previously as a pathogenic variant in one individual reported in the literature (Pigors et al., 2012). The L41P variant was not observed in a significant number of approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The L41P variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position in the beta-sandwich domain of the transglutaminase 5 protein where amino acids with similar properties to Leucine are tolerated across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. While no missense variants in nearby residues have been listed in the Human Gene Mutation Database in association with Acral Peeling Skin Syndrome (Stenson et al., 2014), a number of other missense variants in other regions of the gene have been reported. In summary, the L41P variant is a strong candidate for a pathogenic variant, however the possibility it may be a rare benign variant cannot be excluded.
OMIM RCV000144913 SCV000191915 pathogenic Peeling skin syndrome 2 2012-10-01 no assertion criteria provided literature only

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