Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001237665 | SCV001410433 | uncertain significance | Schimke immuno-osseous dysplasia | 2021-09-01 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine with asparagine at codon 541 of the SMARCAL1 protein (p.Thr541Asn). The threonine residue is weakly conserved and there is a small physicochemical difference between threonine and asparagine. This variant is present in population databases (rs753062232, ExAC 0.001%). This variant has not been reported in the literature in individuals affected with SMARCAL1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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 | RCV002563898 | SCV003530518 | uncertain significance | Inborn genetic diseases | 2022-09-27 | criteria provided, single submitter | clinical testing | The c.1622C>A (p.T541N) alteration is located in exon 9 (coding exon 7) of the SMARCAL1 gene. This alteration results from a C to A substitution at nucleotide position 1622, causing the threonine (T) at amino acid position 541 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |