ClinVar Miner

Submissions for variant NM_001127222.2(CACNA1A):c.6737C>T (p.Ser2246Phe)

gnomAD frequency: 0.00002  dbSNP: rs768312851
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000178595 SCV000230710 uncertain significance not provided 2015-04-13 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001315464 SCV001506039 uncertain significance Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42 2023-10-08 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 2247 of the CACNA1A protein (p.Ser2247Phe). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with CACNA1A-related conditions. ClinVar contains an entry for this variant (Variation ID: 197539). 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 CACNA1A protein function. 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 RCV002515266 SCV003570677 uncertain significance Inborn genetic diseases 2021-08-02 criteria provided, single submitter clinical testing The c.6740C>T (p.S2247F) alteration is located in exon 46 (coding exon 46) of the CACNA1A gene. This alteration results from a C to T substitution at nucleotide position 6740, causing the serine (S) at amino acid position 2247 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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