Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Mendelics | RCV000986216 | SCV001135144 | pathogenic | Deficiency of cytochrome-b5 reductase | 2019-05-28 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001390260 | SCV001591936 | pathogenic | not provided | 2018-05-16 | criteria provided, single submitter | clinical testing | This variant has been observed in individuals affected with recessive congenital methemoglobinemia (RCM) type II (PMID: 15921385, 9266404). ClinVar contains an entry for this variant (Variation ID: 245). For these reasons, this variant has been classified as Pathogenic. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in CYB5R3 are known to be pathogenic (PMID: 18318771). Experimental studies have shown that this intronic change causes aberrant splicing of the CYB5R3 mRNA (PMID: 9266404). This variant is not present in population databases (ExAC no frequency). This sequence change affects an acceptor splice site in intron 5 of the CYB5R3 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. |
Gene |
RCV001390260 | SCV002756852 | likely pathogenic | not provided | 2022-05-05 | criteria provided, single submitter | clinical testing | Canonical splice site variant expected to result in aberrant splicing, and in vitro studies demonstrate altered splicing (Maran et al., 2005); This variant is associated with the following publications: (PMID: 31898843, 25525159, 15921385, 15744830, 9266404) |
Laboratorio de Genetica e Diagnostico Molecular, |
RCV000986216 | SCV003807994 | pathogenic | Deficiency of cytochrome-b5 reductase | 2022-07-05 | criteria provided, single submitter | clinical testing | ACMG classification criteria: PVS1 very strong, PS3 supporting, PS4 moderated, PM2 moderated, PM3 moderated, PP4 |
OMIM | RCV000000269 | SCV000020413 | pathogenic | Methemoglobinemia type 2 | 2005-05-01 | no assertion criteria provided | literature only |