Submissions for variant NM_003227.4(TFR2):c.1235A>T (p.Asn412Ile)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003332066	SCV004039072	uncertain significance	not specified	2023-08-11	criteria provided, single submitter	clinical testing	Variant summary: TFR2 c.1235A>T (p.Asn412Ile) results in a non-conservative amino acid change located in the Peptidase M28 (IPR007484) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 251204 control chromosomes (gnomAD). c.1235A>T has been reported in the literature in an individual(s) affected with Hemochromatosis Type 3 (Bardou_Jacquet_2013). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 23600741, 26799139). No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.
Baylor Genetics	RCV004572935	SCV005053000	likely pathogenic	Hemochromatosis type 3	2024-03-14	criteria provided, single submitter	clinical testing