Submissions for variant NM_005076.5(CNTN2):c.2926G>A (p.Asp976Asn)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002976306	SCV003288075	uncertain significance	Epilepsy, familial adult myoclonic, 5	2022-10-03	criteria provided, single submitter	clinical testing	This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 976 of the CNTN2 protein (p.Asp976Asn). This variant is present in population databases (rs762564380, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with CNTN2-related conditions. 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) performed at Invitae indicates that this missense variant is not expected to disrupt CNTN2 protein function. 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.
Ambry Genetics	RCV004065055	SCV003619054	uncertain significance	not specified	2022-05-18	criteria provided, single submitter	clinical testing	The c.2926G>A (p.D976N) alteration is located in exon 22 (coding exon 21) of the CNTN2 gene. This alteration results from a G to A substitution at nucleotide position 2926, causing the aspartic acid (D) at amino acid position 976 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.