ClinVar Miner

Submissions for variant NM_000346.4(SOX9):c.965G>A (p.Ser322Asn)

gnomAD frequency: 0.00002  dbSNP: rs1239456905
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000519049 SCV000618752 uncertain significance not provided 2017-07-07 criteria provided, single submitter clinical testing The S322N variant in the SOX9 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The S322N variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The S322N variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret S322N as a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV000823160 SCV000964008 uncertain significance Camptomelic dysplasia 2022-08-02 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 322 of the SOX9 protein (p.Ser322Asn). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with SOX9-related conditions. ClinVar contains an entry for this variant (Variation ID: 450200). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SOX9 protein function. 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.

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