NM_017739.4(POMGNT1):c.74_75delinsTT (p.Trp25Phe) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 6, 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:: RCV001998471.6

Allele description [Variation Report for NM_017739.4(POMGNT1):c.74_75delinsTT (p.Trp25Phe)]

NM_017739.4(POMGNT1):c.74_75delinsTT (p.Trp25Phe)

Gene:

POMGNT1:protein O-linked mannose N-acetylglucosaminyltransferase 1 (beta 1,2-) [Gene - OMIM - HGNC]

Variant type:

Indel

Cytogenetic location:

1p34.1

Genomic location:

Preferred name:

NM_017739.4(POMGNT1):c.74_75delinsTT (p.Trp25Phe)

HGVS:

NC_000001.11:g.46197747_46197748delinsAA
NG_009205.3:g.27558_27559delinsTT
NM_001243766.2:c.74_75delinsTT
NM_017739.4:c.74_75delinsTTMANE SELECT
NP_001230695.2:p.Trp25Phe
NP_060209.4:p.Trp25Phe
LRG_701t1:c.74_75delinsTT
LRG_701t2:c.74_75delinsTT
LRG_701:g.27558_27559delinsTT
LRG_701p1:p.Trp25Phe
LRG_701p2:p.Trp25Phe
NC_000001.10:g.46663419_46663420delinsAA
NG_009205.2:g.27558_27559delinsTT

Protein change:

W25F

Links:

dbSNP: rs2148222600

NCBI 1000 Genomes Browser:

rs2148222600

Molecular consequence:

NM_001243766.2:c.74_75delinsTT - missense variant - [Sequence Ontology: SO:0001583]
NM_017739.4:c.74_75delinsTT - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Autosomal recessive limb-girdle muscular dystrophy type 2O
Synonyms:: MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (LIMB-GIRDLE), TYPE C, 3; MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY, LIMB-GIRDLE, POMGNT1-RELATED; Limb-Girdle Muscular Dystrophy Type 3C; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0013161; MedGen: C3150417; Orphanet: 206564; OMIM: 613157

Name:: Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B3 (MDDGB3)
Synonyms:: MUSCULAR DYSTROPHY, CONGENITAL, POMGNT1-RELATED; MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITH IMPAIRED INTELLECTUAL DEVELOPMENT), TYPE B, 3
Identifiers:: MONDO: MONDO:0013155; MedGen: C3150412; OMIM: 613151

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PREDICTED: Macrobrachium nipponense mitochondrial carnitine/acylcarnitine carrie...
PREDICTED: Macrobrachium nipponense mitochondrial carnitine/acylcarnitine carrier protein-like (LOC135216841), mRNA
gi|2708661922|ref|XM_064252350.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002262771	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 6, 2023)	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

SCV002262771

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 6, 2023)

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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002262771.4

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

Description

This sequence change replaces tryptophan with phenylalanine at codon 25 of the POMGNT1 protein (p.Trp25Phe). The tryptophan residue is highly conserved and there is a small physicochemical difference between tryptophan and phenylalanine. This variant is present in population databases (no rsID available, gnomAD 0.0004%). This variant has not been reported in the literature in individuals affected with POMGNT1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1477909). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.

#	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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