NM_001077365.2(POMT1):c.1391G>C (p.Trp464Ser) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 28, 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:: RCV000558807.7

Allele description [Variation Report for NM_001077365.2(POMT1):c.1391G>C (p.Trp464Ser)]

NM_001077365.2(POMT1):c.1391G>C (p.Trp464Ser)

Gene:

POMT1:protein O-mannosyltransferase 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

9q34.13

Genomic location:

Preferred name:

NM_001077365.2(POMT1):c.1391G>C (p.Trp464Ser)

HGVS:

NC_000009.12:g.131518862G>C
NG_008896.1:g.20961G>C
NM_001077365.2:c.1391G>CMANE SELECT
NM_001077366.2:c.1229G>C
NM_001136113.2:c.1391G>C
NM_001136114.2:c.1040G>C
NM_001353193.2:c.1457G>C
NM_001353194.2:c.1229G>C
NM_001353195.2:c.1040G>C
NM_001353196.2:c.1301G>C
NM_001353197.2:c.1295G>C
NM_001353198.2:c.1295G>C
NM_001353199.2:c.1106G>C
NM_001353200.2:c.935G>C
NM_001374689.1:c.1379G>C
NM_001374690.1:c.1365+325G>C
NM_001374691.1:c.1040G>C
NM_001374692.1:c.1040G>C
NM_001374693.1:c.1040G>C
NM_001374695.1:c.1001G>C
NM_007171.4:c.1457G>C
NP_001070833.1:p.Trp464Ser
NP_001070834.1:p.Trp410Ser
NP_001129585.1:p.Trp464Ser
NP_001129586.1:p.Trp347Ser
NP_001340122.2:p.Trp486Ser
NP_001340123.1:p.Trp410Ser
NP_001340124.1:p.Trp347Ser
NP_001340125.1:p.Trp434Ser
NP_001340126.2:p.Trp432Ser
NP_001340127.2:p.Trp432Ser
NP_001340128.2:p.Trp369Ser
NP_001340129.1:p.Trp312Ser
NP_001361618.1:p.Trp460Ser
NP_001361620.1:p.Trp347Ser
NP_001361621.1:p.Trp347Ser
NP_001361622.1:p.Trp347Ser
NP_001361624.1:p.Trp334Ser
NP_009102.3:p.Trp486Ser
NP_009102.4:p.Trp486Ser
LRG_842t1:c.1457G>C
LRG_842t2:c.1391G>C
LRG_842p1:p.Trp486Ser
LRG_842p2:p.Trp464Ser
NC_000009.11:g.134394249G>C
NM_007171.3:c.1457G>C
NR_148391.2:n.1425G>C
NR_148392.2:n.1643G>C
NR_148393.2:n.1564G>C
NR_148394.2:n.1318G>C
NR_148395.2:n.1716G>C
NR_148396.2:n.1350G>C
NR_148397.2:n.1475G>C
NR_148398.2:n.1430G>C
NR_148399.2:n.1956G>C
NR_148400.2:n.1555G>C

Protein change:

W312S

Links:

dbSNP: rs746849558

NCBI 1000 Genomes Browser:

rs746849558

Molecular consequence:

NM_001374690.1:c.1365+325G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001077365.2:c.1391G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001077366.2:c.1229G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001136113.2:c.1391G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001136114.2:c.1040G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353193.2:c.1457G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353194.2:c.1229G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353195.2:c.1040G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353196.2:c.1301G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353197.2:c.1295G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353198.2:c.1295G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353199.2:c.1106G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353200.2:c.935G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001374689.1:c.1379G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001374691.1:c.1040G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001374692.1:c.1040G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001374693.1:c.1040G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001374695.1:c.1001G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_007171.4:c.1457G>C - missense variant - [Sequence Ontology: SO:0001583]
NR_148391.2:n.1425G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_148392.2:n.1643G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_148393.2:n.1564G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_148394.2:n.1318G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_148395.2:n.1716G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_148396.2:n.1350G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_148397.2:n.1475G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_148398.2:n.1430G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_148399.2:n.1956G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_148400.2:n.1555G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Autosomal recessive limb-girdle muscular dystrophy type 2K
Synonyms:: MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (LIMB-GIRDLE), TYPE C, 1; MUSCULAR DYSTROPHY, LIMB-GIRDLE, TYPE 2K; Limb-girdle muscular dystrophy-dystroglycanopathy, type C1
Identifiers:: MONDO: MONDO:0012248; MedGen: C1836373; Orphanet: 86812; OMIM: 609308

Name:: Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1 (MDDGB1)
Synonyms:: MUSCULAR DYSTROPHY, CONGENITAL, POMT1-RELATED; MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITH IMPAIRED INTELLECTUAL DEVELOPMENT), TYPE B, 1
Identifiers:: MONDO: MONDO:0013159; MedGen: C5436962; OMIM: 613155

Name:: Walker-Warburg congenital muscular dystrophy
Synonyms:: Muscular dystrophy-dystroglycanopathy, type A; Walker-Warburg syndrome
Identifiers:: MONDO: MONDO:0000171; MedGen: C0265221; Orphanet: 899; OMIM: PS236670

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000649874	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 28, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 27193224, 28157257, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000649874

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 28, 2023)

germline

clinical testing

PubMed (3)
[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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Analysis of phenotype, enzyme activity and genotype of Chinese patients with POMT1 mutation.

Yang H, Manya H, Kobayashi K, Jiao H, Fu X, Xiao J, Li X, Wang J, Jiang Y, Toda T, Endo T, Wu X, Xiong H.

J Hum Genet. 2016 Aug;61(8):753-9. doi: 10.1038/jhg.2016.42. Epub 2016 May 19.

PubMed [citation]

PMID:: 27193224

Compound heterozygous POMT1 mutations in a Chinese family with autosomal recessive muscular dystrophy-dystroglycanopathy C1.

Hu P, Wu S, Yuan L, Lin Q, Zheng W, Xia H, Xu H, Guan L, Deng H.

J Cell Mol Med. 2017 Jul;21(7):1388-1393. doi: 10.1111/jcmm.13068. Epub 2017 Feb 3.

PubMed [citation]

PMID:: 28157257
PMCID:: PMC5487925

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000649874.4

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

Description

This sequence change replaces tryptophan, which is neutral and slightly polar, with serine, which is neutral and polar, at codon 486 of the POMT1 protein (p.Trp486Ser). This variant is present in population databases (rs746849558, gnomAD 0.007%). This missense change has been observed in individual(s) with muscular dystrophy-dystroglycanopathy (PMID: 27193224, 28157257). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 471375). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt POMT1 protein function. 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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