NM_004977.3(KCNC3):c.1737ACCCCCGCC[1] (p.Pro583_Pro585del) AND not provided

This record was updated by the submitter. Please see the current version.

Germline classification:: Conflicting interpretations of pathogenicity (3 submissions)
Last evaluated:: Aug 24, 2023
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:: RCV000996984.22

Allele description

NM_004977.3(KCNC3):c.1737ACCCCCGCC[1] (p.Pro583_Pro585del)

Gene:

KCNC3:potassium voltage-gated channel subfamily C member 3 [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

19q13.33

Genomic location:

Preferred name:

NM_004977.3(KCNC3):c.1737ACCCCCGCC[1] (p.Pro583_Pro585del)

HGVS:

NC_000019.10:g.50323201CGGGGGTGG[1]
NC_000019.10:g.50323201_50323209CGGGGGTGG[1]
NG_008134.2:g.11162ACCCCCGCC[1]
NM_001372305.1:c.1509ACCCCCGCC[1]
NM_004977.3:c.1737ACCCCCGCC[1]MANE SELECT
NP_001359234.1:p.Pro507_Pro509del
NP_004968.2:p.Pro583_Pro585del
LRG_668t1:c.1737ACCCCCGCC[1]
LRG_668:g.11162ACCCCCGCC[1]
LRG_668p1:p.Pro583_Pro585del
NC_000019.9:g.50826456_50826464del
NC_000019.9:g.50826456_50826464delGGCGGGGGT
NC_000019.9:g.50826458CGGGGGTGG[1]
NM_004977.2:c.1746_1754del

Links:

dbSNP: rs747618525

NCBI 1000 Genomes Browser:

rs747618525

Molecular consequence:

NM_001372305.1:c.1509ACCCCCGCC[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_004977.3:c.1737ACCCCCGCC[1] - inframe_deletion - [Sequence Ontology: SO:0001822]

Observations:

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
SCV001152009	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Likely pathogenic (May 1, 2019)	germline	clinical testing	Citation Link,
SCV002770811	Athena Diagnostics	criteria provided, single submitter (Athena Diagnostics Criteria)	Uncertain significance (Aug 24, 2023)	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 29949095, 26467025
SCV004509506	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Apr 23, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 29949095, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001152009

CeGaT Center for Human Genetics Tuebingen

criteria provided, single submitter

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)

Likely pathogenic
(May 1, 2019)

germline

clinical testing

Citation Link,

SCV002770811

Athena Diagnostics

criteria provided, single submitter

(Athena Diagnostics Criteria)

Uncertain significance
(Aug 24, 2023)

unknown

clinical testing

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

SCV004509506

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Apr 23, 2023)

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	germline	yes	1	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
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

Karbassi I, Maston GA, Love A, DiVincenzo C, Braastad CD, Elzinga CD, Bright AR, Previte D, Zhang K, Rowland CM, McCarthy M, Lapierre JL, Dubois F, Medeiros KA, Batish SD, Jones J, Liaquat K, Hoffman CA, Jaremko M, Wang Z, Sun W, Buller-Burckle A, et al.

Hum Mutat. 2016 Jan;37(1):127-34. doi: 10.1002/humu.22918. Epub 2015 Oct 29.

PubMed [citation]

PMID:: 26467025
PMCID:: PMC4737317

C-terminal proline deletions in KCNC3 cause delayed channel inactivation and an adult-onset progressive SCA13 with spasticity.

Khare S, Galeano K, Zhang Y, Nick JA, Nick HS, Subramony SH, Sampson J, Kaczmarek LK, Waters MF.

Cerebellum. 2018 Oct;17(5):692-697. doi: 10.1007/s12311-018-0950-5.

PubMed [citation]

PMID:: 29949095
PMCID:: PMC8299775

See all PubMed Citations (3)

Details of each submission

From CeGaT Center for Human Genetics Tuebingen, SCV001152009.23

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

#	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		1	not provided	not provided	not provided

From Athena Diagnostics, SCV002770811.2

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

Description

Available data are insufficient to determine the clinical significance of the variant at this time. The frequency of this variant in the general population is higher than would generally be expected for pathogenic variants in this gene (http://gnomad.broadinstitute.org). Assessment of experimental evidence suggests this variant results in abnormal protein function. This variant inhibits current inactivation (PMID: 29949095).

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

From Invitae, SCV004509506.1

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

Description

For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this variant affects KCNC3 function (PMID: 29949095). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. ClinVar contains an entry for this variant (Variation ID: 803573). This variant has been observed in individuals with spinocerebellar ataxia (PMID: 29949095). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs772002798, gnomAD 0.01%). This variant, c.1746_1754del, results in the deletion of 3 amino acid(s) of the KCNC3 protein (p.Pro583_Pro585del), but otherwise preserves the integrity of the reading frame.

#	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: Jun 23, 2024

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