Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Johns Hopkins Genomics, |
RCV003320427 | SCV004024512 | uncertain significance | Bronchiectasis with or without elevated sweat chloride 2 | 2023-05-25 | criteria provided, single submitter | clinical testing | This SCNN1A missense variant (rs200068111) is rare (<0.1%) in a large population dataset (gnomAD v2.1.1: 12/250442 total alleles; 0.005%; no homozygotes). It has not been reported in ClinVar, nor the literature, to our knowledge. Of two bioinformatics tools queried, one predicts that the substitution would be damaging, while the other predicts that it would be tolerated, but these algorithms have low specificity, especially for predicting gain of function variants. The glutamic acid residue at this position is evolutionarily conserved across many of the species assessed, but some species have a different amino acid including two species with glutamine. We consider the clinical significance of c.133G>C in SCNN1A to be uncertain at this time. |
Ambry Genetics | RCV004961258 | SCV005501705 | uncertain significance | Inborn genetic diseases | 2024-09-08 | criteria provided, single submitter | clinical testing | The c.133G>C (p.E45Q) alteration is located in exon 2 (coding exon 1) of the SCNN1A gene. This alteration results from a G to C substitution at nucleotide position 133, causing the glutamic acid (E) at amino acid position 45 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |