Submissions for variant NM_003227.4(TFR2):c.1186C>T (p.Arg396Ter)

gnomAD frequency: 0.00001  dbSNP: rs80338882

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001237605	SCV001410371	pathogenic	Hereditary hemochromatosis	2023-10-28	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg396*) in the TFR2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TFR2 are known to be pathogenic (PMID: 23600741, 26029709). 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 premature translational stop signal has been observed in individual(s) with hemochromatosis (PMID: 16424658, 18450729). ClinVar contains an entry for this variant (Variation ID: 21362). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics	RCV000020534	SCV004203663	pathogenic	Hemochromatosis type 3	2023-10-27	criteria provided, single submitter	clinical testing
GeneReviews	RCV000020534	SCV000041000	not provided	Hemochromatosis type 3		no assertion provided	literature only
Natera, Inc.	RCV000020534	SCV002079940	pathogenic	Hemochromatosis type 3	2020-06-09	no assertion criteria provided	clinical testing