Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000479581 | SCV000573422 | uncertain significance | not provided | 2017-02-28 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the FAM134B gene. The E270A variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The E270A variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The E270A 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 in mammals; however, Alanine is observed at this position in evolution. Missense variants have not been reported in association with neuropathy (Stenson et al., 2014). 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 | RCV004659064 | SCV005162644 | uncertain significance | Inborn genetic diseases | 2024-05-02 | criteria provided, single submitter | clinical testing | The c.809A>C (p.E270A) alteration is located in exon 7 (coding exon 7) of the FAM134B gene. This alteration results from a A to C substitution at nucleotide position 809, causing the glutamic acid (E) at amino acid position 270 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |