NM_176787.5(PIGN):c.1790del (p.Phe597fs) AND Multiple congenital anomalies-hypotonia-seizures syndrome 1

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jan 16, 2024
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:: RCV000855531.3

Allele description [Variation Report for NM_176787.5(PIGN):c.1790del (p.Phe597fs)]

NM_176787.5(PIGN):c.1790del (p.Phe597fs)

Genes:

LOC132090497:Neanderthal introgressed variant-containing enhancer experimental_48690 [Gene]
PIGN:phosphatidylinositol glycan anchor biosynthesis class N [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

18q21.33

Genomic location:

Preferred name:

NM_176787.5(PIGN):c.1790del (p.Phe597fs)

HGVS:

NC_000018.10:g.62105614del
NG_033144.1:g.86445del
NM_012327.6:c.1790del
NM_176787.5:c.1790delMANE SELECT
NP_036459.1:p.Phe597fs
NP_789744.1:p.Phe597fs
NC_000018.9:g.59772845del
NC_000018.9:g.59772847del
NM_176787.4:c.1790delT

Protein change:

F597fs

Links:

dbSNP: rs1599531710

NCBI 1000 Genomes Browser:

rs1599531710

Molecular consequence:

NM_012327.6:c.1790del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_176787.5:c.1790del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Multiple congenital anomalies-hypotonia-seizures syndrome 1 (MCAHS1)
Synonyms:: GLYCOSYLPHOSPHATIDYLINOSITOL BIOSYNTHESIS DEFECT 3; PIGN-CDG; Congenital disorder of glycosylation due to PIGN deficiency
Identifiers:: MONDO: MONDO:0013563; MedGen: C3279775; Orphanet: 280633; OMIM: 614080

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000998748	Institute of Human Genetics, Cologne University	no assertion criteria provided	Likely pathogenic	germline	clinical testing
SCV004626860	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 16, 2024)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 24253414, 27038415, 35179230, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000998748

Institute of Human Genetics, Cologne University

no assertion criteria provided

Likely pathogenic

germline

clinical testing

SCV004626860

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 16, 2024)

germline

clinical testing

PubMed (4)
[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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

PIGN mutations cause congenital anomalies, developmental delay, hypotonia, epilepsy, and progressive cerebellar atrophy.

Ohba C, Okamoto N, Murakami Y, Suzuki Y, Tsurusaki Y, Nakashima M, Miyake N, Tanaka F, Kinoshita T, Matsumoto N, Saitsu H.

Neurogenetics. 2014 May;15(2):85-92. doi: 10.1007/s10048-013-0384-7. Epub 2013 Nov 20. Erratum in: Neurogenetics. 2014 May;15(2):93.

PubMed [citation]

PMID:: 24253414

Fryns Syndrome Associated with Recessive Mutations in PIGN in two Separate Families.

McInerney-Leo AM, Harris JE, Gattas M, Peach EE, Sinnott S, Dudding-Byth T, Rajagopalan S, Barnett CP, Anderson LK, Wheeler L, Brown MA, Leo PJ, Wicking C, Duncan EL.

Hum Mutat. 2016 Jul;37(7):695-702. doi: 10.1002/humu.22994. Epub 2016 May 6.

PubMed [citation]

PMID:: 27038415

See all PubMed Citations (4)

Details of each submission

From Institute of Human Genetics, Cologne University, SCV000998748.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004626860.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change creates a premature translational stop signal (p.Phe597Serfs*11) in the PIGN gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PIGN are known to be pathogenic (PMID: 24253414, 27038415). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with clinical features of PIGN-congenital disorder of glycosylation (PMID: 35179230). ClinVar contains an entry for this variant (Variation ID: 694261). For these reasons, this variant has been 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: Sep 29, 2024

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