NM_000335.5(SCN5A):c.212C>T (p.Pro71Leu) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 7, 2017
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:: RCV003766543.2

Allele description [Variation Report for NM_000335.5(SCN5A):c.212C>T (p.Pro71Leu)]

NM_000335.5(SCN5A):c.212C>T (p.Pro71Leu)

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.212C>T (p.Pro71Leu)

HGVS:

NC_000003.12:g.38633096G>A
NG_008934.1:g.21577C>T
NM_000335.5:c.212C>TMANE SELECT
NM_001099404.2:c.212C>T
NM_001099405.2:c.212C>T
NM_001160160.2:c.212C>T
NM_001160161.2:c.212C>T
NM_001354701.2:c.212C>T
NM_198056.3:c.212C>T
NP_000326.2:p.Pro71Leu
NP_001092874.1:p.Pro71Leu
NP_001092875.1:p.Pro71Leu
NP_001153632.1:p.Pro71Leu
NP_001153633.1:p.Pro71Leu
NP_001341630.1:p.Pro71Leu
NP_932173.1:p.Pro71Leu
NP_932173.1:p.Pro71Leu
LRG_289t1:c.212C>T
LRG_289:g.21577C>T
LRG_289p1:p.Pro71Leu
NC_000003.11:g.38674587G>A
NM_198056.2:c.212C>T

Protein change:

P71L

Links:

dbSNP: rs1060501140

NCBI 1000 Genomes Browser:

rs1060501140

Molecular consequence:

NM_000335.5:c.212C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001099404.2:c.212C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001099405.2:c.212C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001160160.2:c.212C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001160161.2:c.212C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354701.2:c.212C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_198056.3:c.212C>T - missense variant - [Sequence Ontology: SO:0001583]

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
SCV000545061	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 7, 2017)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25348405, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000545061

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 7, 2017)

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

Citations

PubMed

UniProt: a hub for protein information.

UniProt Consortium..

Nucleic Acids Res. 2015 Jan;43(Database issue):D204-12. doi: 10.1093/nar/gku989. Epub 2014 Oct 27.

PubMed [citation]

PMID:: 25348405
PMCID:: PMC4384041

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, SCV000545061.4

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

Description

In summary, this variant is a novel missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. This variant identified in the SCN5A gene is located in the cytoplasmic N-terminal region of the resulting protein (PMID: 25348405). For more information about the location of this variant, please visit www.invitae.com/SCN5A-topology. It is unclear how this variant impacts the function of this protein. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a SCN5A-related disease. This sequence change replaces proline with leucine at codon 71 of the SCN5A protein (p.Pro71Leu). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and leucine.

#	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: Nov 10, 2024

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