ClinVar Miner

Submissions for variant NM_001127222.2(CACNA1A):c.6743C>T (p.Ser2248Leu)

gnomAD frequency: 0.00001  dbSNP: rs1274796380
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002029256 SCV002303953 uncertain significance Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42 2023-03-22 criteria provided, single submitter clinical testing 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) 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. ClinVar contains an entry for this variant (Variation ID: 1514365). This variant has not been reported in the literature in individuals affected with CACNA1A-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 2249 of the CACNA1A protein (p.Ser2249Leu).
Ambry Genetics RCV002548795 SCV003747955 uncertain significance Inborn genetic diseases 2022-06-30 criteria provided, single submitter clinical testing The c.6746C>T (p.S2249L) 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 6746, causing the serine (S) at amino acid position 2249 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
CeGaT Center for Human Genetics Tuebingen RCV003222379 SCV003918071 uncertain significance not provided 2023-08-01 criteria provided, single submitter clinical testing CACNA1A: PM2:Supporting, PP2, PP3

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