Submissions for variant NM_021098.3(CACNA1H):c.1918C>G (p.Pro640Ala)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV002812298	SCV003604909	uncertain significance	Inborn genetic diseases	2022-01-05	criteria provided, single submitter	clinical testing	The c.1918C>G (p.P640A) alteration is located in exon 9 (coding exon 8) of the CACNA1H gene. This alteration results from a C to G substitution at nucleotide position 1918, causing the proline (P) at amino acid position 640 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003331449	SCV004039203	uncertain significance	not specified	2023-08-23	criteria provided, single submitter	clinical testing	Variant summary: CACNA1H c.1918C>G (p.Pro640Ala) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 1.9e-05 in 158824 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1918C>G in individuals affected with Idiopathic Generalized Epilepsy and no experimental evidence demonstrating its impact on protein function have been reported. One submitter has cited a clinical-significance assessment for this variant to ClinVar after 2014 and has classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003777787	SCV004604761	benign	Idiopathic generalized epilepsy; Hyperaldosteronism, familial, type IV	2023-06-14	criteria provided, single submitter	clinical testing