NM_001378969.1(KCND3):c.1256G>A (p.Arg419His) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jul 20, 2021
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:: RCV000420331.2

Allele description [Variation Report for NM_001378969.1(KCND3):c.1256G>A (p.Arg419His)]

NM_001378969.1(KCND3):c.1256G>A (p.Arg419His)

Gene:

KCND3:potassium voltage-gated channel subfamily D member 3 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p13.2

Genomic location:

Preferred name:

NM_001378969.1(KCND3):c.1256G>A (p.Arg419His)

HGVS:

NC_000001.11:g.111786957C>T
NG_032011.2:g.207199G>A
NM_001378969.1:c.1256G>AMANE SELECT
NM_001378970.1:c.1256G>A
NM_004980.5:c.1256G>A
NM_172198.3:c.1256G>A
NP_001365898.1:p.Arg419His
NP_001365899.1:p.Arg419His
NP_004971.2:p.Arg419His
NP_004971.2:p.Arg419His
NP_751948.1:p.Arg419His
LRG_445t1:c.1256G>A
LRG_445:g.207199G>A
LRG_445p1:p.Arg419His
NC_000001.10:g.112329579C>T
NM_004980.4:c.1256G>A

Protein change:

R419H

Links:

dbSNP: rs774338559

NCBI 1000 Genomes Browser:

rs774338559

Molecular consequence:

NM_001378969.1:c.1256G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001378970.1:c.1256G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_004980.5:c.1256G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_172198.3:c.1256G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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
SCV000536443	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Uncertain significance (Mar 7, 2018)	germline	clinical testing	Citation Link,
SCV002501641	AiLife Diagnostics, AiLife Diagnostics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jul 20, 2021)	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

SCV000536443

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Uncertain significance
(Mar 7, 2018)

germline

clinical testing

Citation Link,

SCV002501641

AiLife Diagnostics, AiLife Diagnostics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jul 20, 2021)

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	3	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, SCV000536443.3

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

Description

The R419H variant in the KCND3 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The R419H variant was not observed in approximately 6500 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 R419H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret R419H as a variant of uncertain significance.

#	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 AiLife Diagnostics, AiLife Diagnostics, SCV002501641.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	3	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	yes	not provided	not provided	not provided		3	not provided	not provided	not provided

Last Updated: May 1, 2024

ClinVar

Relating variation to medicine