Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Athena Diagnostics | RCV002505967 | SCV002817276 | pathogenic | not provided | 2019-09-11 | criteria provided, single submitter | clinical testing | This variant is expected to result in the loss of a functional protein. The frequency of this variant in the general population is consistent with pathogenicity (http://gnomad.broadinstitute.org). This variant has been identified in multiple individuals with clinical features associated with this gene (PMID: 8547636, 28520207).This observation is not an independent occurrence and has been identified in the same individual by RCIGM, the other laboratory participating in the GEMINI study. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003388121 | SCV004099755 | pathogenic | Factor XIII, A subunit, deficiency of | 2023-09-12 | criteria provided, single submitter | clinical testing | Variant summary: F13A1 c.27delT (p.Phe9LeufsX67) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 3.6e-05 in 251234 control chromosomes (gnomAD). The variant, c.27delT, has been reported in the literature in multiple homozygous- and compound heterozygous individuals affected with Factor XIIIA Deficiency (e.g. Mikkola_1996, Ivaskevicius_2017, Maron_2021). These data indicate that the variant is very likely to be associated with disease. At least one publication reported that mRNA level of FXlll A-subunit was drastically reduced in patient derived samples (Mikkola_1996), likely due to nonsense mediated decay. The following publications have been ascertained in the context of this evaluation (PMID: 8547636, 28520207, 33587123). One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Mayo Clinic Laboratories, |
RCV002505967 | SCV005413715 | pathogenic | not provided | 2023-10-02 | criteria provided, single submitter | clinical testing | PM2_moderate, PS3, PVS1 |