NM_000335.5(SCN5A):c.3868C>G (p.Leu1290Val) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 5, 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:: RCV003657389.2

Allele description [Variation Report for NM_000335.5(SCN5A):c.3868C>G (p.Leu1290Val)]

NM_000335.5(SCN5A):c.3868C>G (p.Leu1290Val)

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.3868C>G (p.Leu1290Val)

HGVS:

NC_000003.12:g.38562507G>C
NG_008934.1:g.92166C>G
NM_000335.5:c.3868C>GMANE SELECT
NM_001099404.2:c.3871C>G
NM_001099405.2:c.3871C>G
NM_001160160.2:c.3868C>G
NM_001160161.2:c.3709C>G
NM_001354701.2:c.3868C>G
NM_198056.3:c.3871C>G
NP_000326.2:p.Leu1290Val
NP_001092874.1:p.Leu1291Val
NP_001092875.1:p.Leu1291Val
NP_001153632.1:p.Leu1290Val
NP_001153633.1:p.Leu1237Val
NP_001341630.1:p.Leu1290Val
NP_932173.1:p.Leu1291Val
LRG_289:g.92166C>G
NC_000003.11:g.38603998G>C

Protein change:

L1237V

Links:

dbSNP: rs2125844120

NCBI 1000 Genomes Browser:

rs2125844120

Molecular consequence:

NM_000335.5:c.3868C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001099404.2:c.3871C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001099405.2:c.3871C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001160160.2:c.3868C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001160161.2:c.3709C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354701.2:c.3868C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_198056.3:c.3871C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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Xenopus laevis mannose-6-phosphate receptor (cation dependent) L homeolog (m6pr....
Xenopus laevis mannose-6-phosphate receptor (cation dependent) L homeolog (m6pr.L), mRNA
gi|148224928|ref|NM_001087401.1|

Nucleotide
Re/Si-specific NAD(P)(+) transhydrogenase subunit alpha [Scandinavium tedordense...
Re/Si-specific NAD(P)(+) transhydrogenase subunit alpha [Scandinavium tedordense]
gi|2293708585|ref|WP_258965751.1|

Protein
Pseudomonas sp. OTU DN17 16S ribosomal RNA gene, partial sequence
Pseudomonas sp. OTU DN17 16S ribosomal RNA gene, partial sequence
gi|939468478|gb|KT887992.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002156862	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 5, 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

SCV002156862

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 5, 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, SCV002156862.3

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

Description

This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1291 of the SCN5A protein (p.Leu1291Val). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SCN5A-related conditions. ClinVar contains an entry for this variant (Variation ID: 1382658). 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 disruptive. 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.

#	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 3, 2024

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