ClinVar Miner

Submissions for variant NM_001379110.1(SLC9A6):c.1269G>C (p.Lys423Asn)

gnomAD frequency: 0.00002  dbSNP: rs781918578
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel RCV001866179 SCV004808301 benign Christianson syndrome 2024-02-23 reviewed by expert panel curation TThe allele frequency of the p.Lys443Asn variant in SLC9A6 (NM_006359.2) is 0.009% in European (Non-Finnish) sub population in gnomAD v2, which is high enough to meet the BS1 criteria based on thresholds defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like conditions (BS1). The p.Lys443Asn variant is observed in the hemizygous state in at least 2 unaffected individuals (internal database - GeneDx) (BS2). The p.Lys443Asn variant is found in a patient with an alternate molecular basis of disease (internal database - GeneDx) (BP5). In summary, the p.Lys443Asn variant in SLC9A6 is classified as benign based on the ACMG/AMP criteria (BS1, BS2, BP5).
GeneDx RCV001593567 SCV001816627 likely benign not provided 2021-05-19 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001866179 SCV002130061 uncertain significance Christianson syndrome 2023-06-05 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 443 of the SLC9A6 protein (p.Lys443Asn). This variant is present in population databases (rs781918578, gnomAD 0.009%), including at least one homozygous and/or hemizygous individual. ClinVar contains an entry for this variant (Variation ID: 1215092). This variant has not been reported in the literature in individuals affected with SLC9A6-related conditions. 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. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SLC9A6 protein function.

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