Submissions for variant NM_001267550.2(TTN):c.103147G>C (p.Glu34383Gln)

gnomAD frequency: 0.00274  dbSNP: rs148525155

Total submissions: 16

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000118803	SCV000054867	uncertain significance	not provided	2013-06-24	criteria provided, single submitter	research
Genetic Services Laboratory, University of Chicago	RCV000118803	SCV000153430	uncertain significance	not provided	2013-12-23	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000154869	SCV000204551	benign	not specified	2015-08-13	criteria provided, single submitter	clinical testing	p.Glu31815Gln in exon 307 of TTN: This variant is not expected to have clinical significance because it has been identified in 2.5% (166/6612) of Finnish chromo somes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs148525155).
Eurofins Ntd Llc (ga)	RCV000154869	SCV000229382	benign	not specified	2015-03-06	criteria provided, single submitter	clinical testing
GeneDx	RCV000154869	SCV000237909	benign	not specified	2017-04-20	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001086370	SCV000555369	benign	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2024-01-31	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000118803	SCV000844604	benign	not provided	2017-10-25	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000769847	SCV000901273	benign	Cardiomyopathy	2017-02-03	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000154869	SCV001372421	likely benign	not specified	2020-06-10	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002390268	SCV002675227	benign	Cardiovascular phenotype	2018-10-31	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
CeGaT Center for Human Genetics Tuebingen	RCV000118803	SCV003916172	likely benign	not provided	2024-05-01	criteria provided, single submitter	clinical testing	TTN: BS2
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000154869	SCV001739526	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000154869	SCV001921312	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000154869	SCV001957900	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000118803	SCV001970038	likely benign	not provided		no assertion criteria provided	clinical testing
Practice for Gait Abnormalities, David Pomarino, Competency Network Toe Walking c/o Practice Pomarino	RCV002225083	SCV002503606	likely pathogenic	Tip-toe gait		no assertion criteria provided	clinical testing	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.