ClinVar Miner

Submissions for variant NM_001374504.1(TMPRSS6):c.1297G>A (p.Gly433Arg)

gnomAD frequency: 0.00004  dbSNP: rs137853119
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001851548 SCV002211649 pathogenic not provided 2024-11-03 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 442 of the TMPRSS6 protein (p.Gly442Arg). This variant is present in population databases (rs137853119, gnomAD 0.0009%). This missense change has been observed in individuals with iron-refractory iron deficiency anemia (PMID: 18408718, 23319530, 27365303, 27643674). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 1403). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on TMPRSS6 protein function. Experimental studies have shown that this missense change affects TMPRSS6 function (PMID: 19357398, 25588876). For these reasons, this variant has been classified as Pathogenic.
MGZ Medical Genetics Center RCV000001468 SCV002579868 likely pathogenic Iron-refractory iron deficiency anemia 2022-08-17 criteria provided, single submitter clinical testing
OMIM RCV000001468 SCV000021623 pathogenic Iron-refractory iron deficiency anemia 2009-05-28 no assertion criteria provided literature only

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