Submissions for variant NM_021072.4(HCN1):c.2246A>C (p.Gln749Pro)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003823128	SCV004620587	uncertain significance	Early infantile epileptic encephalopathy with suppression bursts	2023-07-09	criteria provided, single submitter	clinical testing	This sequence change replaces glutamine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 749 of the HCN1 protein (p.Gln749Pro). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with HCN1-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 HCN1 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.
3billion, Medical Genetics	RCV004723500	SCV005328788	likely benign	Developmental and epileptic encephalopathy, 24; Generalized epilepsy with febrile seizures plus, type 10	2024-09-20	criteria provided, single submitter	clinical testing	The variant was identified in at least one patient who was diagnosed with a different variant in another gene and showed no symptoms related to the gene containing the variant in question.