ClinVar Miner

Submissions for variant NM_000069.3(CACNA1S):c.3220A>G (p.Thr1074Ala)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV003376519 SCV004085441 uncertain significance Inborn genetic diseases 2023-07-25 criteria provided, single submitter clinical testing The c.3220A>G (p.T1074A) alteration is located in exon 25 (coding exon 25) of the CACNA1S gene. This alteration results from a A to G substitution at nucleotide position 3220, causing the threonine (T) at amino acid position 1074 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV003778057 SCV004568296 uncertain significance Hypokalemic periodic paralysis, type 1; Malignant hyperthermia, susceptibility to, 5 2023-05-26 criteria provided, single submitter clinical testing This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 1074 of the CACNA1S protein (p.Thr1074Ala). This variant has not been reported in the literature in individuals affected with CACNA1S-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) performed at Invitae indicates that this missense variant is not expected to disrupt CACNA1S protein function.

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