Submissions for variant NM_015215.4(CAMTA1):c.4187A>C (p.Asn1396Thr)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV003412574	SCV004123277	uncertain significance	Cerebellar dysfunction with variable cognitive and behavioral abnormalities	2023-07-17	criteria provided, single submitter	clinical testing	The CAMTA1 c.4187A>C p.(Asn1396Thr) missense variant has been identified in a homozygous state in this proband with a phenotype of cerebral palsy and refractory epilepsy and a history of developmental delay prior to development of infantile spasms (PMID: 31957018). This variant is reported in the Genome Aggregation Database in one allele at a frequency of 0.000015 in the European (non-Finnish) population (version 3.1.2). Based on the available evidence, the c.4187A>C p.(Asn1396Thr) variant is classified as a variant of uncertain significance for cerebellar dysfunction with variable cognitive and behavioral abnormalities.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003720910	SCV004516692	uncertain significance	not provided	2023-07-24	criteria provided, single submitter	clinical testing	An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. This missense change has been observed in individual(s) with CAMTA1-related conditions (PMID: 31957018). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces asparagine, which is neutral and polar, with threonine, which is neutral and polar, at codon 1396 of the CAMTA1 protein (p.Asn1396Thr). 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.