NM_000335.5(SCN5A):c.4158G>C (p.Leu1386Phe) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 8, 2023
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:: RCV003557938.2

Allele description [Variation Report for NM_000335.5(SCN5A):c.4158G>C (p.Leu1386Phe)]

NM_000335.5(SCN5A):c.4158G>C (p.Leu1386Phe)

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.4158G>C (p.Leu1386Phe)

HGVS:

NC_000003.12:g.38560231C>G
NG_008934.1:g.94442G>C
NM_000335.5:c.4158G>CMANE SELECT
NM_001099404.2:c.4161G>C
NM_001099405.2:c.4161G>C
NM_001160160.2:c.4158G>C
NM_001160161.2:c.3999G>C
NM_001354701.2:c.4158G>C
NM_198056.3:c.4161G>C
NP_000326.2:p.Leu1386Phe
NP_000326.2:p.Leu1386Phe
NP_001092874.1:p.Leu1387Phe
NP_001092874.1:p.Leu1387Phe
NP_001092875.1:p.Leu1387Phe
NP_001153632.1:p.Leu1386Phe
NP_001153633.1:p.Leu1333Phe
NP_001341630.1:p.Leu1386Phe
NP_932173.1:p.Leu1387Phe
NP_932173.1:p.Leu1387Phe
LRG_289t1:c.4161G>C
LRG_289t2:c.4158G>C
LRG_289t3:c.4161G>C
LRG_289:g.94442G>C
LRG_289p1:p.Leu1387Phe
LRG_289p2:p.Leu1386Phe
LRG_289p3:p.Leu1387Phe
NC_000003.11:g.38601722C>G
NM_000335.4:c.4158G>C
NM_001099404.1:c.4161G>C
NM_198056.2:c.4161G>C
NR_176299.1:n.4907G>C

Protein change:

L1333F

Molecular consequence:

NM_000335.5:c.4158G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001099404.2:c.4161G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001099405.2:c.4161G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001160160.2:c.4158G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001160161.2:c.3999G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354701.2:c.4158G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_198056.3:c.4161G>C - missense variant - [Sequence Ontology: SO:0001583]
NR_176299.1:n.4907G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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tyrosine recombinase XerC [Listeria monocytogenes]
tyrosine recombinase XerC [Listeria monocytogenes]
gi|497597451|ref|WP_009911635.1|

Protein
MULTISPECIES: outer membrane protein [Rhizobium/Agrobacterium group]
MULTISPECIES: outer membrane protein [Rhizobium/Agrobacterium group]
gi|489607998|ref|WP_003512439.1|

Protein
Same Parent, Connectivity for PubChem Compound (Select 10153627) (10)
PubChem Compound
BioProject Links for Protein (Select 2168696710) (2)
BioProject
Taxonomy Links for Protein (Select 2168696750) (1)
Taxonomy

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004305115	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 8, 2023)	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

SCV004305115

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 8, 2023)

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004305115.1

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

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 output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The phenylalanine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant has not been reported in the literature in individuals affected with SCN5A-related conditions. This variant is present in population databases (rs182293857, gnomAD 0.0009%). This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 1387 of the SCN5A protein (p.Leu1387Phe).

#	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: Sep 29, 2024

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