Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV003731983 | SCV004535211 | pathogenic | not provided | 2023-08-04 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. Disruption of this splice site has been observed in individual(s) with iron-refractory iron deficiency anemia (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (no rsID available, gnomAD 0.01%). This sequence change affects a donor splice site in intron 11 of the TMPRSS6 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in TMPRSS6 are known to be pathogenic (PMID: 20232450, 25156943). |
Department of Pathology and Laboratory Medicine, |
RCV005356520 | SCV005918270 | likely pathogenic | Iron-refractory iron deficiency anemia | 2022-11-29 | criteria provided, single submitter | research |