TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17997	54214;54215;54216	chr2:178605188;178605187;178605186	chr2:179469915;179469914;179469913
N2AB	16356	49291;49292;49293	chr2:178605188;178605187;178605186	chr2:179469915;179469914;179469913
N2A	15429	46510;46511;46512	chr2:178605188;178605187;178605186	chr2:179469915;179469914;179469913
N2B	8932	27019;27020;27021	chr2:178605188;178605187;178605186	chr2:179469915;179469914;179469913
Novex-1	9057	27394;27395;27396	chr2:178605188;178605187;178605186	chr2:179469915;179469914;179469913
Novex-2	9124	27595;27596;27597	chr2:178605188;178605187;178605186	chr2:179469915;179469914;179469913
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-114
• Domain position: 30
• Structural Position: 45
• Q(SASA): 0.7112
• Predicted PPI site: I

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
K/N	None	None	1.0	N	0.733	0.293	0.329282125956	gnomAD-4.0.0	4.78292E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.5888E-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
K/A	0.2394	likely_benign	0.2928	benign	-0.08	Destabilizing	0.999	D	0.676	prob.neutral	None	None	None	None	I
K/C	0.6329	likely_pathogenic	0.6883	pathogenic	-0.217	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	I
K/D	0.4843	ambiguous	0.5222	ambiguous	0.156	Stabilizing	1.0	D	0.753	deleterious	None	None	None	None	I
K/E	0.1742	likely_benign	0.1826	benign	0.187	Stabilizing	0.999	D	0.637	neutral	N	0.46931471	None	None	I
K/F	0.7308	likely_pathogenic	0.7805	pathogenic	-0.124	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	I
K/G	0.4491	ambiguous	0.5297	ambiguous	-0.333	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	I
K/H	0.2308	likely_benign	0.2676	benign	-0.641	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	I
K/I	0.26	likely_benign	0.2836	benign	0.518	Stabilizing	1.0	D	0.777	deleterious	None	None	None	None	I
K/L	0.299	likely_benign	0.3549	ambiguous	0.518	Stabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	I
K/M	0.2278	likely_benign	0.2596	benign	0.311	Stabilizing	1.0	D	0.732	prob.delet.	D	0.526480288	None	None	I
K/N	0.3161	likely_benign	0.3518	ambiguous	0.15	Stabilizing	1.0	D	0.733	prob.delet.	N	0.507931813	None	None	I
K/P	0.9165	likely_pathogenic	0.9439	pathogenic	0.349	Stabilizing	1.0	D	0.761	deleterious	None	None	None	None	I
K/Q	0.1169	likely_benign	0.1269	benign	-0.011	Destabilizing	1.0	D	0.709	prob.delet.	N	0.490191414	None	None	I
K/R	0.0865	likely_benign	0.093	benign	-0.153	Destabilizing	0.999	D	0.591	neutral	N	0.487556541	None	None	I
K/S	0.299	likely_benign	0.3447	ambiguous	-0.4	Destabilizing	0.999	D	0.677	prob.neutral	None	None	None	None	I
K/T	0.1109	likely_benign	0.1229	benign	-0.204	Destabilizing	1.0	D	0.731	prob.delet.	N	0.439994667	None	None	I
K/V	0.1903	likely_benign	0.2182	benign	0.349	Stabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	I
K/W	0.7902	likely_pathogenic	0.833	pathogenic	-0.085	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	I
K/Y	0.6323	likely_pathogenic	0.6797	pathogenic	0.244	Stabilizing	1.0	D	0.76	deleterious	None	None	None	None	I

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.