NM_153033.5(KCTD7):c.550C>T (p.Arg184Cys) AND Inborn genetic diseases

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Feb 28, 2024
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:: RCV002513270.3

Allele description [Variation Report for NM_153033.5(KCTD7):c.550C>T (p.Arg184Cys)]

NM_153033.5(KCTD7):c.550C>T (p.Arg184Cys)

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.550C>T (p.Arg184Cys)

HGVS:

NC_000007.14:g.66638912C>T
NG_028110.2:g.15032C>T
NM_001167961.2:c.550C>T
NM_153033.5:c.550C>TMANE SELECT
NP_001161433.1:p.Arg184Cys
NP_694578.1:p.Arg184Cys
NP_694578.1:p.Arg184Cys
LRG_835t1:c.550C>T
LRG_835:g.15032C>T
LRG_835p1:p.Arg184Cys
NC_000007.13:g.66103899C>T
NM_153033.4:c.550C>T
Q96MP8:p.Arg184Cys

Protein change:

R184C; ARG184CYS

Links:

UniProtKB: Q96MP8#VAR_068779; OMIM: 611725.0002; dbSNP: rs387907246

NCBI 1000 Genomes Browser:

rs387907246

Molecular consequence:

NM_001167961.2:c.550C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_153033.5:c.550C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Inborn genetic diseases
Identifiers:: MeSH: D030342; MedGen: C0950123

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003556778	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (Feb 28, 2024)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 22748208, 27742667, 31130284 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003556778

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(Feb 28, 2024)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

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

A homozygous mutation in KCTD7 links neuronal ceroid lipofuscinosis to the ubiquitin-proteasome system.

Staropoli JF, Karaa A, Lim ET, Kirby A, Elbalalesy N, Romansky SG, Leydiker KB, Coppel SH, Barone R, Xin W, MacDonald ME, Abdenur JE, Daly MJ, Sims KB, Cotman SL.

Am J Hum Genet. 2012 Jul 13;91(1):202-8. doi: 10.1016/j.ajhg.2012.05.023. Epub 2012 Jun 28.

PubMed [citation]

PMID:: 22748208
PMCID:: PMC3397260

Pathogenic variants in KCTD7 perturb neuronal K+ fluxes and glutamine transport.

Moen MN, Fjær R, Hamdani EH, Laerdahl JK, Menchini RJ, Vigeland MD, Sheng Y, Undlien DE, Hassel B, Salih MA, El Khashab HY, Selmer KK, Chaudhry FA.

Brain. 2016 Dec;139(Pt 12):3109-3120. Epub 2016 Oct 14.

PubMed [citation]

PMID:: 27742667

See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV003556778.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

The c.550C>T (p.R184C) alteration is located in exon 4 (coding exon 4) of the KCTD7 gene. This alteration results from a C to T substitution at nucleotide position 550, causing the arginine (R) at amino acid position 184 to be replaced by a cysteine (C). Based on data from gnomAD, the T allele has an overall frequency of 0.002% (5/251302) total alleles studied. The highest observed frequency was 0.012% (4/34570) of Latino alleles. This variant has been identified in the homozygous state in multiple individuals with features consistent with KCTD7-related progressive myoclonus epilepsy (Staropoli, 2012; Monies, 2019). This amino acid position is highly conserved in available vertebrate species. This alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this alteration is classified as likely pathogenic.

#	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: May 1, 2024

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