NM_000335.5(SCN5A):c.3266C>T (p.Pro1089Leu) AND not specified

Germline classification:: Benign/Likely benign (6 submissions)
Last evaluated:: Jun 24, 2013
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:: RCV000041614.21

Allele description [Variation Report for NM_000335.5(SCN5A):c.3266C>T (p.Pro1089Leu)]

NM_000335.5(SCN5A):c.3266C>T (p.Pro1089Leu)

Genes:

LOC110121269:VISTA enhancer hs2177 [Gene]
SCN5A:sodium voltage-gated channel alpha subunit 5 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3p22.2

Genomic location:

Preferred name:

NM_000335.5(SCN5A):c.3266C>T (p.Pro1089Leu)

Other names:

p.P1090L:CCG>CTG

HGVS:

NC_000003.12:g.38579455G>A
NG_008934.1:g.75218C>T
NG_053884.1:g.1194G>A
NM_000335.5:c.3266C>TMANE SELECT
NM_001099404.2:c.3269C>T
NM_001099405.2:c.3269C>T
NM_001160160.2:c.3266C>T
NM_001160161.2:c.3228+1476C>T
NM_001354701.2:c.3266C>T
NM_198056.3:c.3269C>T
NP_000326.2:p.Pro1089Leu
NP_001092874.1:p.Pro1090Leu
NP_001092875.1:p.Pro1090Leu
NP_001153632.1:p.Pro1089Leu
NP_001341630.1:p.Pro1089Leu
NP_932173.1:p.Pro1090Leu
NP_932173.1:p.Pro1090Leu
LRG_289t1:c.3269C>T
LRG_289:g.75218C>T
LRG_289p1:p.Pro1090Leu
NC_000003.11:g.38620946G>A
NM_198056.2:c.3269C>T
Q14524:p.Pro1090Leu
c.3269C>T

Protein change:

P1089L

Links:

UniProtKB: Q14524#VAR_014464; dbSNP: rs1805125

NCBI 1000 Genomes Browser:

rs1805125

Molecular consequence:

NM_001160161.2:c.3228+1476C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_000335.5:c.3266C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001099404.2:c.3269C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001099405.2:c.3269C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001160160.2:c.3266C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354701.2:c.3266C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_198056.3:c.3269C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000050839	Biesecker Lab/Clinical Genomics Section, National Institutes of Health - ClinSeq	criteria provided, single submitter (Ng et al. (Circ Cardiovasc Genet. 2013))	Benign (Jun 24, 2013)	unknown	research	PubMed (1) [See all records that cite this PMID]
SCV000065310	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Likely benign (Nov 5, 2012)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000171566	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Benign (Nov 30, 2011)	germline	clinical testing	Citation Link,
SCV001920603	Clinical Genetics, Academic Medical Center - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Benign	germline	clinical testing
SCV001928174	Genome Diagnostics Laboratory, University Medical Center Utrecht - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Benign	germline	clinical testing
SCV001953296	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Benign	germline	clinical testing

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	3	3	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	1	not provided	not provided	not provided	not provided	research
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Interpreting secondary cardiac disease variants in an exome cohort.

Ng D, Johnston JJ, Teer JK, Singh LN, Peller LC, Wynter JS, Lewis KL, Cooper DN, Stenson PD, Mullikin JC, Biesecker LG; NIH Intramural Sequencing Center (NISC) Comparative Sequencing Program..

Circ Cardiovasc Genet. 2013 Aug;6(4):337-46. doi: 10.1161/CIRCGENETICS.113.000039. Epub 2013 Jul 16.

PubMed [citation]

PMID:: 23861362
PMCID:: PMC3887521

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]

PMID:: 24033266
PMCID:: PMC3995020

Details of each submission

From Biesecker Lab/Clinical Genomics Section, National Institutes of Health - ClinSeq, SCV000050839.1

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

#	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		1	not provided	not provided	not provided

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000065310.6

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

Description

Pro1090Leu in exon 18 of SCN5A: This variant is not expected to have clinical si gnificance because it has been identified in 2.1% (12/572) of chromosomes from a broad, though clinically and racially unspecified population from 1000 Genomes Project (http://1000genomes.org; rs1805125). Pro1090Leu in exon 18 of SCN5A (r s1805125; allele frequency = 2.1%, 12/572)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		3	not provided	3	not provided

From GeneDx, SCV000171566.10

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

Description

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

#	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 Clinical Genetics, Academic Medical Center - VKGL Data-share Consensus, SCV001920603.1

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

From Genome Diagnostics Laboratory, University Medical Center Utrecht - VKGL Data-share Consensus, SCV001928174.1

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

From Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus, SCV001953296.1

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

Last Updated: May 19, 2024

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