Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001223812 | SCV001395978 | uncertain significance | Autosomal recessive distal spinal muscular atrophy 2; Amyotrophic lateral sclerosis type 16 | 2019-07-26 | criteria provided, single submitter | clinical testing | 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. 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with SIGMAR1-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This sequence change replaces alanine with glutamic acid at codon 20 of the SIGMAR1 protein (p.Ala20Glu). The alanine residue is moderately conserved and there is a moderate physicochemical difference between alanine and glutamic acid. |
| Ambry Genetics | RCV002563649 | SCV003572163 | uncertain significance | Inborn genetic diseases | 2021-08-12 | criteria provided, single submitter | clinical testing | The c.59C>A (p.A20E) alteration is located in exon 1 (coding exon 1) of the SIGMAR1 gene. This alteration results from a C to A substitution at nucleotide position 59, causing the alanine (A) at amino acid position 20 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |