Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000690963 | SCV000818694 | uncertain significance | Neuropathy, hereditary motor and sensory, type 6B | 2022-07-19 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 137 of the SLC25A46 protein (p.His137Arg). This variant is present in population databases (rs754427464, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with SLC25A46-related conditions. ClinVar contains an entry for this variant (Variation ID: 570160). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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. |
Ambry Genetics | RCV002325379 | SCV002632451 | uncertain significance | Inborn genetic diseases | 2020-10-29 | criteria provided, single submitter | clinical testing | The p.H137R variant (also known as c.410A>G), located in coding exon 4 of the SLC25A46 gene, results from an A to G substitution at nucleotide position 410. The histidine at codon 137 is replaced by arginine, an amino acid with highly similar properties. This alteration has been reported in a compound heterozygous state with a different SLC25A46 alteration in an individual presenting with Parkinson's disease and optic atrophy (Bitetto G et al. Parkinsonism Relat Disord, 2020 05;74:1-5). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |