Submissions for variant NM_003227.4(TFR2):c.2038G>T (p.Asp680Tyr)

dbSNP: rs1302587036

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
BloodGenetics	RCV001794941	SCV002033799	likely pathogenic	Hemochromatosis type 3	2021-07-01	criteria provided, single submitter	research
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001794941	SCV003929319	likely pathogenic	Hemochromatosis type 3	2023-04-28	criteria provided, single submitter	clinical testing	Variant summary: TFR2 c.2038G>T (p.Asp680Tyr) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 152680 control chromosomes (gnomAD). c.2038G>T has been reported in the literature in individuals affected with Hemochromatosis Type 3 (Hernandez_2021). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 34946929). One submitter has provided a clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Based on the evidence outlined above, the variant was classified as likely pathogenic.