Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000519372 | SCV000621420 | uncertain significance | not provided | 2017-10-06 | criteria provided, single submitter | clinical testing | The G657A variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The G657A variant is observed in 2/23830 (0.008%) alleles from individuals of African background (Lek et al., 2016). This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. However, the G657A variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
| Labcorp Genetics |
RCV003766972 | SCV004634409 | uncertain significance | Pitt-Hopkins-like syndrome 2 | 2024-09-03 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 657 of the NRXN1 protein (p.Gly657Ala). This variant is present in population databases (rs780931684, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with NRXN1-related conditions. ClinVar contains an entry for this variant (Variation ID: 452601). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. |