Submissions for variant NM_000334.4(SCN4A):c.1173del (p.Phe392fs)

dbSNP: rs1235665641

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV001267295	SCV001445476	pathogenic	Inborn genetic diseases	2018-06-29	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000722954	SCV001476052	likely pathogenic	not provided	2019-12-31	criteria provided, single submitter	clinical testing	The variant results in a shift of the reading frame, and is therefore predicted to result in the loss of a functional protein. Not found in the total gnomAD dataset, and the data is high quality.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001862125	SCV002228137	pathogenic	Hyperkalemic periodic paralysis	2023-10-14	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Phe392Serfs*12) in the SCN4A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SCN4A are known to be pathogenic (PMID: 26700687). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SCN4A-related conditions. ClinVar contains an entry for this variant (Variation ID: 591772). For these reasons, this variant has been classified as Pathogenic.
Revvity Omics, Revvity	RCV000722954	SCV003812606	likely pathogenic	not provided	2022-11-10	criteria provided, single submitter	clinical testing
GeneDx	RCV000722954	SCV005332818	likely pathogenic	not provided	2024-02-06	criteria provided, single submitter	clinical testing	Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 26700687)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004782530	SCV005395220	pathogenic	Congenital myopathy 22A, classic	2024-09-23	criteria provided, single submitter	clinical testing	Variant summary: SCN4A c.1173delC (p.Phe392SerfsX12) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 221764 control chromosomes. To our knowledge, no occurrence of c.1173delC in individuals affected with Congenital Myopathy 22A, Classic and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 591772). Based on the evidence outlined above, the variant was classified as pathogenic.
Fulgent Genetics, Fulgent Genetics	RCV005021126	SCV005650903	likely pathogenic	Potassium-aggravated myotonia; Paramyotonia congenita of Von Eulenburg; Hypokalemic periodic paralysis, type 2; Hyperkalemic periodic paralysis; Congenital myasthenic syndrome 16; Congenital myopathy 22A, classic; Congenital myopathy 22B, severe fetal	2024-04-08	criteria provided, single submitter	clinical testing
Gharavi Laboratory, Columbia University	RCV000722954	SCV000854085	uncertain significance	not provided	2018-09-16	no assertion criteria provided	research