TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19013	57262;57263;57264	chr2:178598580;178598579;178598578	chr2:179463307;179463306;179463305
N2AB	17372	52339;52340;52341	chr2:178598580;178598579;178598578	chr2:179463307;179463306;179463305
N2A	16445	49558;49559;49560	chr2:178598580;178598579;178598578	chr2:179463307;179463306;179463305
N2B	9948	30067;30068;30069	chr2:178598580;178598579;178598578	chr2:179463307;179463306;179463305
Novex-1	10073	30442;30443;30444	chr2:178598580;178598579;178598578	chr2:179463307;179463306;179463305
Novex-2	10140	30643;30644;30645	chr2:178598580;178598579;178598578	chr2:179463307;179463306;179463305
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Fn3-26
• Domain position: 26
• Structural Position: 28
• Q(SASA): 0.7209
• 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
L/P	rs991075111	None	0.896	N	0.291	0.201	0.589813230912	gnomAD-4.0.0	3.43309E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	4.50202E-06	0	0
L/V	None	-0.141	0.002	N	0.103	0.065	0.115124310173	gnomAD-2.1.1	4.11E-06	None	None	None	None	I	None	0	0	None	1.00766E-04	0	None	0	None	0	0	0
L/V	None	-0.141	0.002	N	0.103	0.065	0.115124310173	gnomAD-4.0.0	2.05983E-06	None	None	None	None	I	None	0	0	None	7.6864E-05	0	None	0	0	0	0	1.66168E-05

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
L/A	0.1442	likely_benign	0.1597	benign	-0.617	Destabilizing	0.25	N	0.296	neutral	None	None	None	None	I
L/C	0.5157	ambiguous	0.5159	ambiguous	-0.792	Destabilizing	0.977	D	0.235	neutral	None	None	None	None	I
L/D	0.5654	likely_pathogenic	0.5886	pathogenic	-0.104	Destabilizing	0.85	D	0.285	neutral	None	None	None	None	I
L/E	0.2849	likely_benign	0.2728	benign	-0.158	Destabilizing	0.617	D	0.327	neutral	None	None	None	None	I
L/F	0.1534	likely_benign	0.1651	benign	-0.502	Destabilizing	0.85	D	0.265	neutral	None	None	None	None	I
L/G	0.3669	ambiguous	0.401	ambiguous	-0.787	Destabilizing	0.447	N	0.299	neutral	None	None	None	None	I
L/H	0.2603	likely_benign	0.2511	benign	0.063	Stabilizing	0.992	D	0.221	neutral	None	None	None	None	I
L/I	0.0824	likely_benign	0.0867	benign	-0.274	Destabilizing	0.08	N	0.29	neutral	N	0.479173839	None	None	I
L/K	0.2747	likely_benign	0.2348	benign	-0.367	Destabilizing	0.021	N	0.253	neutral	None	None	None	None	I
L/M	0.0978	likely_benign	0.1099	benign	-0.604	Destabilizing	0.85	D	0.289	neutral	None	None	None	None	I
L/N	0.2633	likely_benign	0.3055	benign	-0.29	Destabilizing	0.85	D	0.279	neutral	None	None	None	None	I
L/P	0.2159	likely_benign	0.213	benign	-0.358	Destabilizing	0.896	D	0.291	neutral	N	0.473399873	None	None	I
L/Q	0.1316	likely_benign	0.1277	benign	-0.429	Destabilizing	0.81	D	0.297	neutral	N	0.486387813	None	None	I
L/R	0.266	likely_benign	0.2199	benign	0.113	Stabilizing	0.681	D	0.284	neutral	N	0.475016026	None	None	I
L/S	0.1724	likely_benign	0.1864	benign	-0.754	Destabilizing	0.021	N	0.241	neutral	None	None	None	None	I
L/T	0.163	likely_benign	0.1801	benign	-0.696	Destabilizing	0.021	N	0.179	neutral	None	None	None	None	I
L/V	0.0767	likely_benign	0.0857	benign	-0.358	Destabilizing	0.002	N	0.103	neutral	N	0.467071334	None	None	I
L/W	0.3097	likely_benign	0.2738	benign	-0.515	Destabilizing	0.992	D	0.295	neutral	None	None	None	None	I
L/Y	0.3363	likely_benign	0.3551	ambiguous	-0.289	Destabilizing	0.92	D	0.254	neutral	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.