Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Genetic Services Laboratory, |
RCV000500256 | SCV000597590 | pathogenic | Congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome | 2016-08-01 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001008131 | SCV001167890 | pathogenic | not provided | 2023-01-13 | criteria provided, single submitter | clinical testing | Frameshift variant predicted to result in protein truncation, as the last 17 amino acids are replaced with 8 different amino acids, and other loss-of-function variants have been reported downstream at GeneDx; This variant is associated with the following publications: (PMID: 26494905, 29358286, 25193871) |
| Invitae | RCV000500256 | SCV001207039 | pathogenic | Congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome | 2024-01-22 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Ser418Lysfs*9) in the TRNT1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 17 amino acid(s) of the TRNT1 protein. This variant is present in population databases (rs758671550, gnomAD 0.05%). This premature translational stop signal has been observed in individuals with TRNT1-related conditions (PMID: 25193871, 26494905, 29358286; Invitae). It has also been observed to segregate with disease in related individuals. This variant is also known as c.1246A[8]. ClinVar contains an entry for this variant (Variation ID: 234934). For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003226259 | SCV003922452 | likely pathogenic | TRNT1-Related Disorders | 2023-03-26 | criteria provided, single submitter | clinical testing | Variant summary: TRNT1 c.1252dupA (p.Ser418LysfsX9) located in the last exon results in a premature termination codon, predicted to cause a truncation of the encoded protein and expected to disrupt the last 17 amino acid(s) of the TRNT1 protein. The variant allele was found at a frequency of 0.00028 in 250732 control chromosomes. This frequency des not allow conclusions about variant significance. c.1252dupA has been reported in the literature in individuals affected with TRNT1-Related Disorders, as a biallelic compound heterozygous genotype in at-least two individuals with features of congenital sideroblastic anaemia with immunodeficiency, fevers and developmental delay (SIFD) and as a different variant (1246delA, p.S418fs) resulting in a frameshift at Ser418 in three individuals with molecularly uncharacterized RP (example, Chakraborty_2014, DeLuca_2016, Giannelou_2018). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| OMIM | RCV000223673 | SCV000280023 | pathogenic | Retinitis pigmentosa and erythrocytic microcytosis | 2016-05-26 | no assertion criteria provided | literature only |