NM_001267550.2(TTN):c.69130C>T (p.Pro23044Ser) AND Tip-toe gait

Germline classification:: no classifications from unflagged records (1 submission)
Last evaluated:: Apr 29, 2025
Review status:: no classifications from unflagged records

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:: RCV002222367.14

Allele description [Variation Report for NM_001267550.2(TTN):c.69130C>T (p.Pro23044Ser)]

NM_001267550.2(TTN):c.69130C>T (p.Pro23044Ser)

Genes:

TTN-AS1:TTN antisense RNA 1 [Gene - HGNC]
TTN:titin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q31.2

Genomic location:

Preferred name:

NM_001267550.2(TTN):c.69130C>T (p.Pro23044Ser)

Other names:

p.P20476S:CCA>TCA

HGVS:

NC_000002.12:g.178577205G>A
NG_011618.3:g.258598C>T
NG_051363.1:g.59379G>A
NM_001256850.1:c.64207C>T
NM_001267550.2:c.69130C>TMANE SELECT
NM_003319.4:c.41935C>T
NM_133378.4:c.61426C>T
NM_133432.3:c.42310C>T
NM_133437.4:c.42511C>T
NP_001243779.1:p.Pro21403Ser
NP_001254479.2:p.Pro23044Ser
NP_003310.4:p.Pro13979Ser
NP_596869.4:p.Pro20476Ser
NP_597676.3:p.Pro14104Ser
NP_597681.4:p.Pro14171Ser
LRG_391t1:c.69130C>T
LRG_391:g.258598C>T
NC_000002.11:g.179441932G>A
NM_001267550.1:c.69130C>T
Q8WZ42:p.Pro21403Ser
c.61426C>T

Protein change:

P13979S

Links:

UniProtKB: Q8WZ42#VAR_040219; dbSNP: rs55980498

Molecular consequence:

NM_001256850.1:c.64207C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001267550.2:c.69130C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_003319.4:c.41935C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_133378.4:c.61426C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_133432.3:c.42310C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_133437.4:c.42511C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Tip-toe gait
Synonyms:: Toe walking
Identifiers:: MedGen: C0427144; Human Phenotype Ontology: HP:0030051

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

No clinical assertions found. See "Flagged submissions" below.

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

Citations

PubMed

NGS-Panel Diagnosis Developed for the Differential Diagnosis of Idiopathic Toe Walking and Its Application for the Investigation of Possible Genetic Causes for the Gait Anomaly.

Pomarino D, Emelina A, Heidrich J, Rostásy K, Schirmer S, Schönfeldt JO, Thren A, Wagner F, Thren JR, Berger N.

Glob Med Genet. 2023 Jun;10(2):63-71. doi: 10.1055/s-0043-57230.

PubMed [citation]

PMID:: 37091313
PMCID:: PMC10121371

Details of each submission

From Practice for Gait Abnormalities, David Pomarino, Competency Network Toe Walking C/o Practice Pomarino, SCV002500840.3

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

Description

Myopathy refers to diseases that affect skeletal Muscles. These diseases attack muscle fibers, making muscles weak. Inherited myopathies are often caused by inheriting an abnormal gene mutation from a parent that causes the disease. Symptoms of congenital myopathies usually start at birth or in early childhood, but may not appear until the teen years or even later in adulthood. Congenital myopathies are somewhat unique compared with other inherited myopathies, as weakness typically affects all muscles and is often not progressive. Symptoms are: Muscle weakness, most commonly of upper arms and shoulders and thighs, muscle cramps, stiffness and spasms, fatigue with exertion and lack of energy. Our patients all walk on tiptoe, so they show similar symptoms. When we genetically test them with our toe walking panel, we find that around 90 per cent of them have a genetic variant that explains their toe walking. These can be assigned, for example, to the area of myopathies (such as variants of the COL6A3 gene), the area of hereditary neuropathies (such as variants of the KMT2C gene) or the area of metabolic diseases (such as variants of the PYGM gene). In a smaller group of patients with almost identical symptoms, no abnormality is found in the genes of our panel, but spastic paraplegia can be detected. In another small group of our toe walkers, no abnormalities can be detected in the genes analysed in our toe walking panel, nor do they suffer from spastic paraplegia, as is also the case with healthy children. In contrast to these, however, they show a tiptoe gait. These patients suffer from infantile cerebral palsy, in which toe walking can also be observed.

#	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

Flagged submissions

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002500840	Practice for Gait Abnormalities, David Pomarino, Competency Network Toe Walking C/o Practice Pomarino	flagged submission Reason: Outlier claim with insufficient supporting evidence Notes: None	Likely pathogenic	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

SCV002500840

Practice for Gait Abnormalities, David Pomarino, Competency Network Toe Walking C/o Practice Pomarino

flagged submission

Reason: Outlier claim with insufficient supporting evidence

Notes: None

Likely pathogenic

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Last Updated: Jul 6, 2026

ClinVar

Relating variation to medicine