ClinVar Miner

Submissions for variant NM_000069.3(CACNA1S):c.1723C>T (p.Leu575Phe)

gnomAD frequency: 0.00001  dbSNP: rs772213240
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000811642 SCV000951918 uncertain significance Hypokalemic periodic paralysis, type 1; Malignant hyperthermia, susceptibility to, 5 2023-12-09 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 575 of the CACNA1S protein (p.Leu575Phe). This variant is present in population databases (rs772213240, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with CACNA1S-related conditions. ClinVar contains an entry for this variant (Variation ID: 655458). 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 expected to disrupt CACNA1S protein function with a positive 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.
GeneDx RCV002462175 SCV002756759 uncertain significance not provided 2022-05-16 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Genome-Nilou Lab RCV003453699 SCV004179009 uncertain significance Malignant hyperthermia, susceptibility to, 5 2023-04-11 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV003453700 SCV004179010 uncertain significance Thyrotoxic periodic paralysis, susceptibility to, 1 2023-04-11 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV003458542 SCV004179011 uncertain significance Congenital myopathy 18 2023-04-11 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV003456149 SCV004179012 uncertain significance Hypokalemic periodic paralysis, type 1 2023-04-11 criteria provided, single submitter clinical testing
Ambry Genetics RCV004028736 SCV004915024 uncertain significance Inborn genetic diseases 2023-10-24 criteria provided, single submitter clinical testing The c.1723C>T (p.L575F) alteration is located in exon 12 (coding exon 12) of the CACNA1S gene. This alteration results from a C to T substitution at nucleotide position 1723, causing the leucine (L) at amino acid position 575 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV005012351 SCV005631208 uncertain significance Hypokalemic periodic paralysis, type 1; Malignant hyperthermia, susceptibility to, 5; Thyrotoxic periodic paralysis, susceptibility to, 1; Congenital myopathy 18 2024-04-04 criteria provided, single submitter clinical testing

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