ClinVar Miner

Submissions for variant NM_001161352.2(KCNMA1):c.2122C>T (p.Arg708Trp)

gnomAD frequency: 0.00004  dbSNP: rs200299051
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
New York Genome Center RCV001291678 SCV001480259 uncertain significance Generalized epilepsy-paroxysmal dyskinesia syndrome 2019-09-13 criteria provided, single submitter clinical testing The c.2122C>T (p.Arg708Trp) variant identified in the KCNMA1 gene substitutes a moderately conserved Arginine for Tryptophan at amino acid 708/1237 (coding exon19/28). This variant is found with low frequency in gnomAD (2 heterozygotes, 0 homozygotes; allele frequency: 1.06e-5) and ExAC (1 heterozygote, 0 homozygotes; allele frequency: 4.67e-5), suggesting it is not a common benign variant in the populations represented in these databases. In silico algorithms do not agree on the effect of this variant, as it is predicted both Neutral (Provean;score: -0.98) and Damaging (SIFT; score: 0.021) to the function of the canonical transcript. This variant is absent from ClinVar and to our current knowledge has not been reported in affected individuals in the literature, although it is located within the intracellular C-terminus where many other variants have been reported in affected individuals [PMID: 31427379]. Given the lack of evidence supporting pathogenicity of the c.2122C>T (p.Arg708Trp) variant identified in the KCNMA1 gene it is reported here as a Variant of Uncertain Significance.
PreventionGenetics, part of Exact Sciences RCV004738230 SCV005352824 uncertain significance KCNMA1-related disorder 2024-07-09 no assertion criteria provided clinical testing The KCNMA1 c.2122C>T variant is predicted to result in the amino acid substitution p.Arg708Trp. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0026% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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