ClinVar Miner

Submissions for variant NM_006946.4(SPTBN2):c.1973G>A (p.Arg658Gln)

gnomAD frequency: 0.00001  dbSNP: rs753491527
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV006465528 SCV007353434 uncertain significance not provided 2026-01-27 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 658 of the SPTBN2 protein (p.Arg658Gln). This variant is present in population databases (rs753491527, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with SPTBN2-related conditions. ClinVar contains an entry for this variant (Variation ID: 915288). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt SPTBN2 protein function with a negative predictive value of 80%. 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.
Ambry Genetics RCV005742171 SCV006434556 uncertain significance Inborn genetic diseases 2025-06-24 criteria provided, single submitter clinical testing The c.1973G>A (p.R658Q) alteration is located in exon 14 (coding exon 13) of the SPTBN2 gene. This alteration results from a G to A substitution at nucleotide position 1973, causing the arginine (R) at amino acid position 658 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Baylor Genetics RCV001169870 SCV001528666 uncertain significance Spinocerebellar ataxia type 5 2018-05-30 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Genomic Research Center, Shahid Beheshti University of Medical Sciences RCV001169870 SCV001251779 likely benign Spinocerebellar ataxia type 5 2020-05-03 criteria provided, single submitter clinical testing

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