NM_021072.4(HCN1):c.-25_425del (p.Met1_Arg142del) AND Early infantile epileptic encephalopathy with suppression bursts

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 21, 2019
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV001247201.2

Allele description [Variation Report for NM_021072.4(HCN1):c.-25_425del (p.Met1_Arg142del)]

NM_021072.4(HCN1):c.-25_425del (p.Met1_Arg142del)

Gene:

HCN1:hyperpolarization activated cyclic nucleotide gated potassium channel 1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

5p12

Genomic location:

Preferred name:

NM_021072.4(HCN1):c.-25_425del (p.Met1_Arg142del)

HGVS:

NC_000005.10:g.45695670_45696119del
NG_042183.1:g.5001_5450del
NM_021072.4:c.-25_425delMANE SELECT
NP_066550.2:p.Met1_Arg142del
NC_000005.9:g.45695772_45696221del
NM_021072.3:c.-25_425del

Links:

dbSNP: rs1739994846

NCBI 1000 Genomes Browser:

rs1739994846

Molecular consequence:

NM_021072.4:c.-25_425del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_021072.4:c.-25_425del - initiator_codon_variant - [Sequence Ontology: SO:0001582]

Condition(s)

Name:: Early infantile epileptic encephalopathy with suppression bursts (EIEE)
Synonyms:: Early infantile epileptic encephalopathy; Ohtahara syndrome; Developmental and epileptic encephalopathy
Identifiers:: MONDO: MONDO:0100062; MedGen: C0393706; Orphanet: 1934; OMIM: PS308350

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001420609	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 21, 2019)	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

SCV001420609

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 21, 2019)

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV001420609.2

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

Description

This sequence change deletes 224 nucleotides from exon 1 of the HCN1 mRNA (c.-190_224del), affecting the initiator methionine. While it is expected to result in an absent or disrupted protein product, alternate in-frame methionines downstream of the initiator codon could potentially rescue the translation initiation. This variant has not been reported in the literature in individuals with HCN1-related disease. The current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in HCN1 cause disease. 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.

#	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: Sep 3, 2023

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