Submissions for variant NM_001374504.1(TMPRSS6):c.406G>A (p.Glu136Lys)

gnomAD frequency: 0.00230  dbSNP: rs116310349

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV001144179	SCV001304759	likely benign	Microcytic anemia	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Invitae	RCV002557075	SCV003269801	benign	not provided	2023-05-13	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003413952	SCV004116095	uncertain significance	TMPRSS6-related condition	2023-05-26	criteria provided, single submitter	clinical testing	The TMPRSS6 c.433G>A variant is predicted to result in the amino acid substitution p.Glu145Lys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.70% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/22-37492129-C-T). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.