Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001864393 | SCV002130120 | uncertain significance | not provided | 2025-01-16 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg299Alafs*4) in the LETM1 gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in LETM1 cause disease. This variant is present in population databases (rs775607436, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with LETM1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1370872). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV005238027 | SCV005887490 | uncertain significance | not specified | 2025-01-24 | criteria provided, single submitter | clinical testing | Variant summary: LETM1 c.888_889delAG (p.Arg299AlafsX4) 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, however current evidence is not sufficient to establish loss of function as a mechanism for disease. The variant allele was found at a frequency of 0.00016 in 251046 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in LETM1 causing Neurodegeneration, Childhood-Onset, With Multisystem Involvement Due To Mitochondrial Dysfunction, allowing no conclusion about variant significance. To our knowledge, no occurrence of c.888_889delAG in individuals affected with Neurodegeneration, Childhood-Onset, With Multisystem Involvement Due To Mitochondrial Dysfunction and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 1370872). Based on the evidence outlined above, the variant was classified as uncertain significance. |