Submissions for variant NM_018100.4(EFHC1):c.1057C>T (p.Arg353Trp)

gnomAD frequency: 0.00013  dbSNP: rs527295360

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000187358	SCV000240943	uncertain significance	not provided	2015-07-23	criteria provided, single submitter	clinical testing	The R353W missense change was previously reported in three members of an Italian family, two of whom had classic juvenile myoclonic epilepsy and the other had idiopathic generalized epilepsy with grand mal tonic- clonic seizures (Annesi et al., 2007). 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 R353W variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, it alters a poorly conserved position in the second DM10 domain of the EFHC1 gene and in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. The variant is found in EPILEPSY,CHILD-EPI panel(s).
Labcorp Genetics (formerly Invitae), Labcorp	RCV001836748	SCV000640919	likely benign	Absence seizure; Myoclonic epilepsy, juvenile, susceptibility to, 1	2025-01-15	criteria provided, single submitter	clinical testing
Experimental Epileptology, AG Lerche, Hertie Institute for Clinical Brain Research	RCV001808466	SCV002059213	benign	Seizure	2022-01-02	criteria provided, single submitter	research	ACMG/AMP criteria: PP3, BP6, BS1, BS4
New York Genome Center	RCV001836748	SCV002097681	uncertain significance	Absence seizure; Myoclonic epilepsy, juvenile, susceptibility to, 1	2020-06-12	criteria provided, single submitter	clinical testing