TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17990	54193;54194;54195	chr2:178605209;178605208;178605207	chr2:179469936;179469935;179469934
N2AB	16349	49270;49271;49272	chr2:178605209;178605208;178605207	chr2:179469936;179469935;179469934
N2A	15422	46489;46490;46491	chr2:178605209;178605208;178605207	chr2:179469936;179469935;179469934
N2B	8925	26998;26999;27000	chr2:178605209;178605208;178605207	chr2:179469936;179469935;179469934
Novex-1	9050	27373;27374;27375	chr2:178605209;178605208;178605207	chr2:179469936;179469935;179469934
Novex-2	9117	27574;27575;27576	chr2:178605209;178605208;178605207	chr2:179469936;179469935;179469934
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-114
• Domain position: 23
• Structural Position: 35
• Q(SASA): 0.0807
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
V/A	None	None	0.977	N	0.609	0.647	0.723663604452	gnomAD-4.0.0	3.60103E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.93757E-06	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
V/A	0.8911	likely_pathogenic	0.9136	pathogenic	-1.205	Destabilizing	0.977	D	0.609	neutral	N	0.489509129	None	None	N
V/C	0.9477	likely_pathogenic	0.9578	pathogenic	-0.679	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
V/D	0.9985	likely_pathogenic	0.9988	pathogenic	-1.271	Destabilizing	0.999	D	0.867	deleterious	None	None	None	None	N
V/E	0.9957	likely_pathogenic	0.9963	pathogenic	-1.341	Destabilizing	0.999	D	0.857	deleterious	D	0.605267103	None	None	N
V/F	0.7367	likely_pathogenic	0.7677	pathogenic	-1.183	Destabilizing	0.995	D	0.846	deleterious	None	None	None	None	N
V/G	0.9675	likely_pathogenic	0.9761	pathogenic	-1.448	Destabilizing	0.999	D	0.862	deleterious	D	0.567888594	None	None	N
V/H	0.9978	likely_pathogenic	0.9983	pathogenic	-1.101	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
V/I	0.0842	likely_benign	0.084	benign	-0.663	Destabilizing	0.15	N	0.237	neutral	None	None	None	None	N
V/K	0.9967	likely_pathogenic	0.9976	pathogenic	-1.07	Destabilizing	0.998	D	0.859	deleterious	None	None	None	None	N
V/L	0.6626	likely_pathogenic	0.6933	pathogenic	-0.663	Destabilizing	0.898	D	0.621	neutral	D	0.53635528	None	None	N
V/M	0.6349	likely_pathogenic	0.6544	pathogenic	-0.385	Destabilizing	0.993	D	0.801	deleterious	D	0.604863494	None	None	N
V/N	0.9944	likely_pathogenic	0.995	pathogenic	-0.686	Destabilizing	0.999	D	0.897	deleterious	None	None	None	None	N
V/P	0.998	likely_pathogenic	0.9985	pathogenic	-0.809	Destabilizing	0.999	D	0.865	deleterious	None	None	None	None	N
V/Q	0.995	likely_pathogenic	0.9959	pathogenic	-0.951	Destabilizing	0.999	D	0.888	deleterious	None	None	None	None	N
V/R	0.994	likely_pathogenic	0.9957	pathogenic	-0.476	Destabilizing	0.999	D	0.89	deleterious	None	None	None	None	N
V/S	0.9769	likely_pathogenic	0.9779	pathogenic	-1.06	Destabilizing	0.998	D	0.851	deleterious	None	None	None	None	N
V/T	0.9192	likely_pathogenic	0.9221	pathogenic	-1.035	Destabilizing	0.983	D	0.69	prob.neutral	None	None	None	None	N
V/W	0.9966	likely_pathogenic	0.9974	pathogenic	-1.321	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
V/Y	0.978	likely_pathogenic	0.9823	pathogenic	-1.053	Destabilizing	0.999	D	0.847	deleterious	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.