Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV005282405 | SCV005947152 | uncertain significance | Inborn genetic diseases | 2025-02-18 | criteria provided, single submitter | clinical testing | The c.3368G>A (p.R1123Q) alteration is located in exon 22 (coding exon 22) of the SMC1A gene. This alteration results from a G to A substitution at nucleotide position 3368, causing the arginine (R) at amino acid position 1123 to be replaced by a glutamine (Q). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). Other variant(s) at the same codon, c.3367C>T (p.R1123W), have been identified in individual(s) with features consistent with SMC1A-related Cornelia de Lange syndrome (Liu, 2009). This amino acid position is highly conserved in available vertebrate species. This missense alteration is located in a region that has a low rate of benign missense variation (Lek, 2016; Firth, 2009). The in silico prediction for this alteration is inconclusive. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |