Submissions for variant NM_001267550.2(TTN):c.17818T>C (p.Cys5940Arg)

gnomAD frequency: 0.00012  dbSNP: rs374882815

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000154992	SCV000204674	uncertain significance	not specified	2013-08-30	criteria provided, single submitter	clinical testing	The Cys4696Arg variant in TTN has not been previously reported in individuals wi th cardiomyopathy, but has been identified in 1/8200 European American chromosom es by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/). Co mputational analyses (biochemical amino acid properties, conservation, AlignGVGD , PolyPhen2, and SIFT) do not provide strong support for or against an impact to the protein. Additional information is needed to fully assess the clinical sign ificance of this variant.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000228841	SCV000286467	uncertain significance	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2017-11-29	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000247714	SCV000318452	uncertain significance	Cardiovascular phenotype	2013-03-06	criteria provided, single submitter	clinical testing	There is insufficient or conflicting evidence for classification of this alteration.
Eurofins Ntd Llc (ga)	RCV000713979	SCV000704299	uncertain significance	not provided	2016-12-20	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000713979	SCV000844634	uncertain significance	not provided	2017-12-01	criteria provided, single submitter	clinical testing
Practice for Gait Abnormalities, David Pomarino, Competency Network Toe Walking c/o Practice Pomarino	RCV001353378	SCV001548540	uncertain significance	Tip-toe gait	2021-01-29	criteria provided, single submitter	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.
GeneDx	RCV000713979	SCV002504308	likely benign	not provided	2020-01-22	criteria provided, single submitter	clinical testing	See Variant Classification Assertion Criteria.
Revvity Omics, Revvity	RCV000713979	SCV003818369	uncertain significance	not provided	2020-03-15	criteria provided, single submitter	clinical testing
Clinical Genetics, Academic Medical Center	RCV000713979	SCV001921947	uncertain significance	not provided		no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000713979	SCV001963401	uncertain significance	not provided		no assertion criteria provided	clinical testing