TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18166	54721;54722;54723	chr2:178604191;178604190;178604189	chr2:179468918;179468917;179468916
N2AB	16525	49798;49799;49800	chr2:178604191;178604190;178604189	chr2:179468918;179468917;179468916
N2A	15598	47017;47018;47019	chr2:178604191;178604190;178604189	chr2:179468918;179468917;179468916
N2B	9101	27526;27527;27528	chr2:178604191;178604190;178604189	chr2:179468918;179468917;179468916
Novex-1	9226	27901;27902;27903	chr2:178604191;178604190;178604189	chr2:179468918;179468917;179468916
Novex-2	9293	28102;28103;28104	chr2:178604191;178604190;178604189	chr2:179468918;179468917;179468916
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Fn3-20
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.5196
• 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/F	rs878953621	None	0.623	N	0.51	0.167	0.402043589563	gnomAD-4.0.0	6.84993E-07	None	None	None	None	I	None	2.99563E-05	0	None	0	0	None	0	0	0	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
L/A	0.2486	likely_benign	0.2503	benign	-0.61	Destabilizing	0.134	N	0.49	neutral	None	None	None	None	I
L/C	0.5281	ambiguous	0.5411	ambiguous	-0.59	Destabilizing	0.892	D	0.566	neutral	None	None	None	None	I
L/D	0.7463	likely_pathogenic	0.7544	pathogenic	-0.021	Destabilizing	0.519	D	0.833	deleterious	None	None	None	None	I
L/E	0.4078	ambiguous	0.4182	ambiguous	-0.123	Destabilizing	0.519	D	0.797	deleterious	None	None	None	None	I
L/F	0.2735	likely_benign	0.2688	benign	-0.708	Destabilizing	0.623	D	0.51	neutral	N	0.513320911	None	None	I
L/G	0.5587	ambiguous	0.5647	pathogenic	-0.758	Destabilizing	0.519	D	0.685	prob.delet.	None	None	None	None	I
L/H	0.3211	likely_benign	0.3244	benign	-0.078	Destabilizing	0.95	D	0.815	deleterious	N	0.463287254	None	None	I
L/I	0.13	likely_benign	0.1253	benign	-0.35	Destabilizing	0.104	N	0.507	neutral	N	0.46279609	None	None	I
L/K	0.2332	likely_benign	0.2593	benign	-0.177	Destabilizing	0.519	D	0.623	neutral	None	None	None	None	I
L/M	0.154	likely_benign	0.162	benign	-0.302	Destabilizing	0.687	D	0.52	neutral	None	None	None	None	I
L/N	0.427	ambiguous	0.4496	ambiguous	0.027	Stabilizing	0.519	D	0.835	deleterious	None	None	None	None	I
L/P	0.1246	likely_benign	0.1288	benign	-0.404	Destabilizing	0.002	N	0.414	neutral	N	0.372675518	None	None	I
L/Q	0.1717	likely_benign	0.1728	benign	-0.232	Destabilizing	0.687	D	0.845	deleterious	None	None	None	None	I
L/R	0.2161	likely_benign	0.2119	benign	0.364	Stabilizing	0.449	N	0.836	deleterious	N	0.46027586	None	None	I
L/S	0.3643	ambiguous	0.3624	ambiguous	-0.457	Destabilizing	0.134	N	0.529	neutral	None	None	None	None	I
L/T	0.2504	likely_benign	0.2258	benign	-0.451	Destabilizing	0.002	N	0.322	neutral	None	None	None	None	I
L/V	0.1204	likely_benign	0.1206	benign	-0.404	Destabilizing	0.104	N	0.457	neutral	N	0.421581399	None	None	I
L/W	0.4817	ambiguous	0.4468	ambiguous	-0.693	Destabilizing	0.962	D	0.829	deleterious	None	None	None	None	I
L/Y	0.4284	ambiguous	0.4349	ambiguous	-0.42	Destabilizing	0.687	D	0.518	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.