NM_018100.4(EFHC1):c.1856T>G (p.Ile619Ser) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jun 2, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000187374.15

Allele description [Variation Report for NM_018100.4(EFHC1):c.1856T>G (p.Ile619Ser)]

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

Gene:

EFHC1:EF-hand domain containing 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6p12.2

Genomic location:

Preferred name:

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

Other names:

p.I619S:ATC>AGC

HGVS:

NC_000006.12:g.52492274T>G
NG_016760.1:g.77079T>G
NM_001172420.2:c.1799T>G
NM_018100.4:c.1856T>GMANE SELECT
NP_001165891.1:p.Ile600Ser
NP_060570.2:p.Ile619Ser
NC_000006.11:g.52357072T>G
NM_018100.3:c.1856T>G
NR_033327.2:n.3182T>G

Protein change:

I600S

Links:

dbSNP: rs142458862

NCBI 1000 Genomes Browser:

rs142458862

Molecular consequence:

NM_001172420.2:c.1799T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_018100.4:c.1856T>G - missense variant - [Sequence Ontology: SO:0001583]
NR_033327.2:n.3182T>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000240959	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Uncertain significance (May 16, 2013)	germline	clinical testing	Citation Link,
SCV004234677	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jun 2, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000240959

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Uncertain significance
(May 16, 2013)

germline

clinical testing

Citation Link,

SCV004234677

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jun 2, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From GeneDx, SCV000240959.11

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

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).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Revvity Omics, Revvity, SCV004234677.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Dec 14, 2025

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