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NM_001136271.3(NKX2-6):c.478C>T (p.Pro160Ser) AND Conotruncal heart malformations

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jun 20, 2020
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:
RCV001299524.1

Allele description

NM_001136271.3(NKX2-6):c.478C>T (p.Pro160Ser)

Gene:
NKX2-6:NK2 homeobox 6 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
8p21.2
Genomic location:
Preferred name:
NM_001136271.3(NKX2-6):c.478C>T (p.Pro160Ser)
HGVS:
  • NC_000008.11:g.23702879G>A
  • NG_030636.1:g.8720C>T
  • NM_001136271.3:c.478C>TMANE SELECT
  • NP_001129743.2:p.Pro160Ser
  • NC_000008.10:g.23560392G>A
Protein change:
P160S
Links:
dbSNP: rs1461236642
NCBI 1000 Genomes Browser:
rs1461236642
Molecular consequence:
  • NM_001136271.3:c.478C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Conotruncal heart malformations (CTHM)
Synonyms:
Conotruncal cardiac defects
Identifiers:
MONDO: MONDO:0016581; MedGen: C1857586; Orphanet: 3384; Orphanet: 3426; OMIM: 217095

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001488620Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Jun 20, 2020) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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 Invitae, SCV001488620.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

This sequence change replaces proline with serine at codon 160 of the NKX2-6 protein (p.Pro160Ser). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and serine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with NKX2-6-related conditions. 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Apr 23, 2022