Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV000049983 | SCV000404365 | uncertain significance | Mulibrey nanism syndrome | 2017-04-28 | criteria provided, single submitter | clinical testing | The TRIM37 c.745C>T (p.Gln249Ter) variant is a stop-gained variant that is predicted to cause premature truncation of the protein. The p.Gln249Ter variant has been reported in one study in which it was found in one individual with Mulibrey nanism in a compound heterozygous state with a frameshift variant (Hamalainen et al. 2004). The p.Gln249Ter variant was absent from 95 controls and is not found in the 1000 Genomes Project, the Exome Sequencing Project, or the Exome Aggregation Consortium despite being in a region of good coverage. Due to the potential impact of stop-gained variants and supporting evidence, this variant is classified as a variant of unknown significance but suspicious for pathogenicity for Mulibrey nanism. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |
Baylor Genetics | RCV000049983 | SCV004204316 | pathogenic | Mulibrey nanism syndrome | 2023-05-15 | criteria provided, single submitter | clinical testing | |
Invitae | RCV003556136 | SCV004297496 | pathogenic | not provided | 2023-02-05 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln249*) in the TRIM37 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TRIM37 are known to be pathogenic (PMID: 10888877, 15108285). This variant is present in population databases (rs386834005, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with mulibrey nanism (PMID: 15108285). ClinVar contains an entry for this variant (Variation ID: 56570). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
Juha Muilu Group; Institute for Molecular Medicine Finland |
RCV000049983 | SCV000082392 | probable-pathogenic | Mulibrey nanism syndrome | no assertion criteria provided | not provided | Converted during submission to Likely pathogenic. |