Submissions for variant NM_018100.4(EFHC1):c.1856T>G (p.Ile619Ser)

gnomAD frequency: 0.00006  dbSNP: rs142458862

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000187374	SCV000240959	uncertain significance	not provided	2013-05-16	criteria provided, single submitter	clinical testing	The Ile619Ser missense change has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The amino acid substitution is non-conservative, as a non-polar Isoleucine residue is replaced by a polar Serine residue. It alters a conserved position in the C-terminal region of the protein, and multiple in silico algorithms predict it may be damaging to protein structure/function. However, missense mutations have not been reported in this region of the protein in association with epilepsy. Therefore, based on the currently available information, it is unclear whether Ile619Ser is a disease-causing mutation or a rare benign variant. The variant is found in EPILEPSY panel(s).
Labcorp Genetics (formerly Invitae), Labcorp	RCV003765188	SCV001008647	likely benign	Absence seizure; Myoclonic epilepsy, juvenile, susceptibility to, 1	2024-11-18	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000187374	SCV004234677	uncertain significance	not provided	2022-06-02	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003927737	SCV004743362	likely benign	EFHC1-related disorder	2020-08-24	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).