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NM_176787.5(PIGN):c.601_602insT (p.Glu201fs) AND Multiple congenital anomalies-hypotonia-seizures syndrome 1

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jul 18, 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:
RCV003642020.2

Allele description [Variation Report for NM_176787.5(PIGN):c.601_602insT (p.Glu201fs)]

NM_176787.5(PIGN):c.601_602insT (p.Glu201fs)

Gene:
PIGN:phosphatidylinositol glycan anchor biosynthesis class N [Gene - OMIM - HGNC]
Variant type:
Insertion
Cytogenetic location:
18q21.33
Genomic location:
Preferred name:
NM_176787.5(PIGN):c.601_602insT (p.Glu201fs)
HGVS:
  • NC_000018.10:g.62148286_62148287insA
  • NG_033144.1:g.43770_43771insT
  • NG_033144.2:g.43769_43770insT
  • NM_012327.6:c.601_602insT
  • NM_176787.5:c.601_602insTMANE SELECT
  • NP_036459.1:p.Glu201fs
  • NP_789744.1:p.Glu201fs
  • NC_000018.9:g.59815519_59815520insA
Protein change:
E201fs
Molecular consequence:
  • NM_012327.6:c.601_602insT - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_176787.5:c.601_602insT - 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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004525604Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Jul 18, 2023) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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 (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004525604.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant has not been reported in the literature in individuals affected with PIGN-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu201Valfs*32) 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).

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

Last Updated: Sep 29, 2024