NM_004387.4(NKX2-5):c.280C>T (p.Pro94Ser) AND Atrial septal defect 7

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 24, 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:: RCV000549035.6

Allele description [Variation Report for NM_004387.4(NKX2-5):c.280C>T (p.Pro94Ser)]

NM_004387.4(NKX2-5):c.280C>T (p.Pro94Ser)

Gene:

NKX2-5:NK2 homeobox 5 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

5q35.1

Genomic location:

Preferred name:

NM_004387.4(NKX2-5):c.280C>T (p.Pro94Ser)

HGVS:

NC_000005.10:g.173234804G>A
NG_013340.1:g.5509C>T
NM_001166175.2:c.280C>T
NM_001166176.2:c.280C>T
NM_004387.4:c.280C>TMANE SELECT
NP_001159647.1:p.Pro94Ser
NP_001159648.1:p.Pro94Ser
NP_004378.1:p.Pro94Ser
LRG_671t1:c.280C>T
LRG_671:g.5509C>T
LRG_671p1:p.Pro94Ser
NC_000005.9:g.172661807G>A
NM_004387.3:c.280C>T

Protein change:

P94S

Links:

dbSNP: rs1009994744

NCBI 1000 Genomes Browser:

rs1009994744

Molecular consequence:

NM_001166175.2:c.280C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001166176.2:c.280C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_004387.4:c.280C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Atrial septal defect 7
Synonyms:: Atrial septal defect with atrioventricular conduction defects; ASD WITH OR WITHOUT ATRIOVENTRICULAR CONDUCTION DEFECTS; Atrial septal defect 7 with or without atrioventricular conduction defects; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0007173; MedGen: C3276096; Orphanet: 1479; OMIM: 108900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000644775	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Apr 24, 2017)	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

SCV000644775

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Apr 24, 2017)

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):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV000644775.4

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

Description

In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a NKX2-5-related disease. This sequence change replaces proline with serine at codon 94 of the NKX2-5 protein (p.Pro94Ser). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and serine.

#	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: Feb 28, 2024

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