Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002360368 | SCV002654441 | uncertain significance | Inborn genetic diseases | 2022-01-07 | criteria provided, single submitter | clinical testing | The p.W406R variant (also known as c.1216T>C), located in coding exon 9 of the SLC12A6 gene, results from a T to C substitution at nucleotide position 1216. The tryptophan at codon 406 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Molecular Genetics, |
RCV003994429 | SCV004812884 | uncertain significance | Charcot-Marie-Tooth disease | 2023-11-05 | criteria provided, single submitter | clinical testing | This sequence change in SLC12A6 is predicted to replace tryptophan with arginine at codon 406, p.(Trp406Arg). The tryptophan residue is highly conserved (100 vertebrates, UCSC), and is located in the extracellular domain. There is a large physicochemical difference between tryptophan and arginine. The variant is present in a single European non-Finnish individual in the population database gnomAD v2.1 (1/113,713 alleles). To our knowledge, this variant has not been previously reported in the relevant scientific literature. Computational evidence is uninformative for the missense substitution (REVEL = 0.567). Based on the classification scheme RMH Modified ACMG/AMP Guidelines v1.6.1, this variant is classified as a VARIANT OF UNCERTAIN SIGNIFICANCE. Following criteria are met: PM2_Supporting |