ClinVar Miner

Submissions for variant NM_021098.3(CACNA1H):c.4780_4781delinsTT (p.Ala1594Phe)

dbSNP: rs1555518356
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000537560 SCV000632174 uncertain significance Idiopathic generalized epilepsy; Hyperaldosteronism, familial, type IV 2022-04-18 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 1594 of the CACNA1H protein (p.Ala1594Phe). 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 CACNA1H-related conditions. ClinVar contains an entry for this variant (Variation ID: 460126). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Not Available"). 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 RCV000658444 SCV000780216 uncertain significance not provided 2018-05-23 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the CACNA1H gene. The c.4780_4781delGCinsTT variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The c.4780_4781delGCinsTT variant is observed in 11/11210 (0.1%) alleles from individuals of East Asian background in large population cohorts (Lek et al., 2016). The c.4780_4781delGCinsTT variant results in an in-frame change of a single Alanine residue to a Phenylalanine residue, denoted p.Ala1594Phe. The c.4780_4781delGCinsTT variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Fulgent Genetics, Fulgent Genetics RCV002490983 SCV002781663 uncertain significance Epilepsy, childhood absence, susceptibility to, 6; Hyperaldosteronism, familial, type IV 2021-10-15 criteria provided, single submitter clinical testing

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