NM_007059.4(KPTN):c.714_731dup (p.Gln246_Asp247insMetTrpSerValLeuGln) AND Inborn genetic diseases

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 10, 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:: RCV003343637.2

Allele description [Variation Report for NM_007059.4(KPTN):c.714_731dup (p.Gln246_Asp247insMetTrpSerValLeuGln)]

NM_007059.4(KPTN):c.714_731dup (p.Gln246_Asp247insMetTrpSerValLeuGln)

Gene:

KPTN:kaptin, actin binding protein [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

19q13.32

Genomic location:

Preferred name:

NM_007059.4(KPTN):c.714_731dup (p.Gln246_Asp247insMetTrpSerValLeuGln)

HGVS:

NC_000019.10:g.47479922_47479939dup
NG_034097.1:g.9329_9346dup
NM_001291296.2:c.546_563dup
NM_007059.4:c.714_731dupMANE SELECT
NP_001278225.1:p.Gln190_Asp191insMetTrpSerValLeuGln
NP_008990.2:p.Gln246_Asp247insMetTrpSerValLeuGln
NC_000019.9:g.47983175_47983176insACCGACCACATCTGCAGA
NC_000019.9:g.47983179_47983196dup
NM_007059.2:c.714_731dupTCTGCAGATGTGGTCGGT
NM_007059.3:c.714_731dup
NR_111923.2:n.860_877dup

Links:

OMIM: 615620.0002; dbSNP: rs587777148

NCBI 1000 Genomes Browser:

rs587777148

Molecular consequence:

NM_001291296.2:c.546_563dup - inframe_insertion - [Sequence Ontology: SO:0001821]
NM_007059.4:c.714_731dup - inframe_insertion - [Sequence Ontology: SO:0001821]
NR_111923.2:n.860_877dup - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Inborn genetic diseases
Identifiers:: MeSH: D030342; MedGen: C0950123

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004058227	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Jul 10, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 24239382, 30008475, 32358097 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004058227

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Jul 10, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

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

Mutations in KPTN cause macrocephaly, neurodevelopmental delay, and seizures.

Baple EL, Maroofian R, Chioza BA, Izadi M, Cross HE, Al-Turki S, Barwick K, Skrzypiec A, Pawlak R, Wagner K, Coblentz R, Zainy T, Patton MA, Mansour S, Rich P, Qualmann B, Hurles ME, Kessels MM, Crosby AH.

Am J Hum Genet. 2014 Jan 2;94(1):87-94. doi: 10.1016/j.ajhg.2013.10.001. Epub 2013 Nov 14.

PubMed [citation]

PMID:: 24239382
PMCID:: PMC3882725

Clinical genome sequencing in an unbiased pediatric cohort.

Thiffault I, Farrow E, Zellmer L, Berrios C, Miller N, Gibson M, Caylor R, Jenkins J, Faller D, Soden S, Saunders C.

Genet Med. 2019 Feb;21(2):303-310. doi: 10.1038/s41436-018-0075-8. Epub 2018 Jul 16.

PubMed [citation]

PMID:: 30008475
PMCID:: PMC6752301

See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV004058227.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

The c.714_731dup18 (p.M241_Q246dup) alteration, located in coding exon 8 of the KPTN gene, results from an in-frame duplication of 18 nucleotides at_x000D_ positions 714 to 731. This results in the duplication of 6 amino acids from codons 241 to 246. Based on data from gnomAD, this allele has an overall frequency of 0.048% (135/279060) total alleles studied. The highest observed frequency was 0.101% (25/24646) of European (Finnish) alleles. This alteration was reported in trans with a second KPTN alteration in multiple individuals with features consistent with KPTN-related neurodevelopmental disorder (Baple, 2014; Thiffault, 2019; Thiffault, 2020). Functional analysis demonstrated that the p.M241_Q246dup alteration led to a mislocalized kaptin protein (Baple, 2014). This alteration is predicted to be deleterious by in silico analysis (Choi, 2012). Based on the available evidence, this alteration is classified as pathogenic.

#	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 18, 2024

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