Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000384736 | SCV000330836 | pathogenic | not provided | 2016-09-20 | criteria provided, single submitter | clinical testing | The S36G variant in the DNM1L gene has previously been reported in two siblings with slowly progressive infantile encephalopathy who were also compound heterozygous for a frameshift variant in DNM1L (Nasca et al., 2016). Introduction of the S36G variant into DNM1 deficient S. cerevisiae found that S36G is associated with reduced oxygen consumption, respiratory activity, and COX activity compared to wildtype (Nasca et al., 2016). Additional functional studies found that S36G is also associated with abnormal mitochondrial fission (Nasca et al., 2016). The S36G variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations The S36G variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, we interpret S36G to be a pathogenic variant. |
| Labcorp Genetics |
RCV000384736 | SCV004295859 | uncertain significance | not provided | 2023-12-01 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 36 of the DNM1L protein (p.Ser36Gly). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with autosomal recessive encephalopathy (PMID: 27328748). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 253266). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. |
| OMIM | RCV000239716 | SCV000298169 | pathogenic | Encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1 | 2016-08-25 | no assertion criteria provided | literature only |