Submissions for variant NM_001161352.2(KCNMA1):c.36CGG[10] (p.Gly18_Gly20dup)

dbSNP: rs760628050

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001043326	SCV001207059	uncertain significance	Generalized epilepsy-paroxysmal dyskinesia syndrome	2024-09-12	criteria provided, single submitter	clinical testing	This variant, c.48_56dup, results in the insertion of 3 amino acid(s) of the KCNMA1 protein (p.Gly18_Gly20dup), but otherwise preserves the integrity of the reading frame. 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 KCNMA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 841161). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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.
CeGaT Center for Human Genetics Tuebingen	RCV001171770	SCV001334619	likely benign	not provided	2020-03-01	criteria provided, single submitter	clinical testing
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV001043326	SCV001369942	uncertain significance	Generalized epilepsy-paroxysmal dyskinesia syndrome	2018-12-06	criteria provided, single submitter	clinical testing	This variant was classified as: Uncertain significance. The available evidence on this variant's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in classifying this variant: No criteria apply.
GeneDx	RCV001171770	SCV002512849	uncertain significance	not provided	2022-04-21	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; In-frame insertion of 3 amino acids in a repetitive region with no known function
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004587020	SCV005076845	uncertain significance	not specified	2024-04-09	criteria provided, single submitter	clinical testing	Variant summary: KCNMA1 c.48_56dupCGGCGGCGG (p.Gly18_Gly20dup) results in an in-frame duplication that is predicted to duplicate 3 amino acids into the encoded protein. The variant was absent in 114424 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.48_56dupCGGCGGCGG in individuals affected with Paroxysmal Nonkinesigenic Dyskinesia, 3, With Or Without Generalized Epilepsy and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 841161). Based on the evidence outlined above, the variant was classified as uncertain significance.