Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000235370 | SCV000294197 | uncertain significance | not provided | 2016-06-06 | criteria provided, single submitter | clinical testing | The M4348L variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It 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. However, the M4348L variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position where amino acids with similar properties to Methionine are tolerated across species, and Leucine is observed at this position in other species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
Ambry Genetics | RCV002379054 | SCV002689871 | uncertain significance | Inborn genetic diseases | 2020-07-16 | criteria provided, single submitter | clinical testing | The p.M4348L variant (also known as c.13042A>C), located in coding exon 73 of the DYNC1H1 gene, results from an A to C substitution at nucleotide position 13042. The methionine at codon 4348 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Institute for Clinical Genetics, |
RCV000235370 | SCV004026268 | uncertain significance | not provided | 2023-02-16 | criteria provided, single submitter | clinical testing |