NM_153033.5(KCTD7):c.335G>A (p.Arg112His) AND Progressive myoclonic epilepsy type 3

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Feb 21, 2020
Review status:: criteria provided, conflicting classifications

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:: RCV000761541.10

Allele description [Variation Report for NM_153033.5(KCTD7):c.335G>A (p.Arg112His)]

NM_153033.5(KCTD7):c.335G>A (p.Arg112His)

Gene:

KCTD7:potassium channel tetramerization domain containing 7 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7q11.21

Genomic location:

Preferred name:

NM_153033.5(KCTD7):c.335G>A (p.Arg112His)

Other names:

p.R112H:CGC>CAC

HGVS:

NC_000007.14:g.66638273G>A
NG_028110.2:g.14393G>A
NM_001167961.2:c.335G>A
NM_153033.5:c.335G>AMANE SELECT
NP_001161433.1:p.Arg112His
NP_694578.1:p.Arg112His
NP_694578.1:p.Arg112His
LRG_835t1:c.335G>A
LRG_835:g.14393G>A
LRG_835p1:p.Arg112His
NC_000007.13:g.66103260G>A
NM_153033.4:c.335G>A

Protein change:

R112H

Links:

dbSNP: rs774026720

NCBI 1000 Genomes Browser:

rs774026720

Molecular consequence:

NM_001167961.2:c.335G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_153033.5:c.335G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Progressive myoclonic epilepsy type 3
Synonyms:: EPILEPSY, PROGRESSIVE MYOCLONIC, 3, WITH OR WITHOUT INTRACELLULAR INCLUSIONS; CEROID LIPOFUSCINOSIS, NEURONAL, 14; EPILEPSY, PROGRESSIVE MYOCLONIC, 3, WITHOUT INTRACELLULAR INCLUSIONS
Identifiers:: MONDO: MONDO:0012721; MedGen: C2673257; Orphanet: 263516; OMIM: 611726

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000891686	Department Of Genetics, Sultan Qaboos University Hospital, Sultan Qaboos University	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Dec 30, 2017)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001493420	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 21, 2020)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 29655203, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000891686

Department Of Genetics, Sultan Qaboos University Hospital, Sultan Qaboos University

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Dec 30, 2017)

unknown

clinical testing

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

SCV001493420

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 21, 2020)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	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

Diagnostic outcomes for genetic testing of 70 genes in 8565 patients with epilepsy and neurodevelopmental disorders.

Lindy AS, Stosser MB, Butler E, Downtain-Pickersgill C, Shanmugham A, Retterer K, Brandt T, Richard G, McKnight DA.

Epilepsia. 2018 May;59(5):1062-1071. doi: 10.1111/epi.14074. Epub 2018 Apr 14.

PubMed [citation]

PMID:: 29655203

See all PubMed Citations (3)

Details of each submission

From Department Of Genetics, Sultan Qaboos University Hospital, Sultan Qaboos University, SCV000891686.1

#	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	unknown	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Invitae, SCV001493420.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been observed in individual(s) with clinical features of epilepsy and neurodevelopmental disorders (PMID: 29655203). ClinVar contains an entry for this variant (Variation ID: 206015). This variant is present in population databases (rs774026720, ExAC 0.001%). This sequence change replaces arginine with histidine at codon 112 of the KCTD7 protein (p.Arg112His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine.

#	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: Feb 28, 2024

ClinVar

Relating variation to medicine