TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13735	41428;41429;41430	chr2:178636524;178636523;178636522	chr2:179501251;179501250;179501249
N2AB	12094	36505;36506;36507	chr2:178636524;178636523;178636522	chr2:179501251;179501250;179501249
N2A	11167	33724;33725;33726	chr2:178636524;178636523;178636522	chr2:179501251;179501250;179501249
N2B	4670	14233;14234;14235	chr2:178636524;178636523;178636522	chr2:179501251;179501250;179501249
Novex-1	4795	14608;14609;14610	chr2:178636524;178636523;178636522	chr2:179501251;179501250;179501249
Novex-2	4862	14809;14810;14811	chr2:178636524;178636523;178636522	chr2:179501251;179501250;179501249
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-87
• Domain position: 52
• Structural Position: 125
• Q(SASA): 0.3862
• 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
I/S	None	None	0.669	N	0.433	0.205	0.699732275208	gnomAD-4.0.0	6.84328E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99598E-07	0	0
I/T	rs2060462916	None	0.005	N	0.164	0.069	0.579627256647	gnomAD-4.0.0	1.36866E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.7992E-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
I/A	0.792	likely_pathogenic	0.8216	pathogenic	-1.805	Destabilizing	0.525	D	0.348	neutral	None	None	None	None	I
I/C	0.9813	likely_pathogenic	0.981	pathogenic	-0.886	Destabilizing	0.998	D	0.434	neutral	None	None	None	None	I
I/D	0.9814	likely_pathogenic	0.9848	pathogenic	-1.523	Destabilizing	0.949	D	0.497	neutral	None	None	None	None	I
I/E	0.938	likely_pathogenic	0.9412	pathogenic	-1.528	Destabilizing	0.949	D	0.505	neutral	None	None	None	None	I
I/F	0.3681	ambiguous	0.3936	ambiguous	-1.289	Destabilizing	0.934	D	0.405	neutral	N	0.503918272	None	None	I
I/G	0.9719	likely_pathogenic	0.9812	pathogenic	-2.127	Highly Destabilizing	0.842	D	0.473	neutral	None	None	None	None	I
I/H	0.9071	likely_pathogenic	0.9231	pathogenic	-1.388	Destabilizing	0.998	D	0.476	neutral	None	None	None	None	I
I/K	0.9301	likely_pathogenic	0.9314	pathogenic	-1.362	Destabilizing	0.842	D	0.491	neutral	None	None	None	None	I
I/L	0.2824	likely_benign	0.2911	benign	-0.985	Destabilizing	0.005	N	0.113	neutral	N	0.476653018	None	None	I
I/M	0.2708	likely_benign	0.267	benign	-0.639	Destabilizing	0.934	D	0.453	neutral	N	0.510958047	None	None	I
I/N	0.8531	likely_pathogenic	0.8804	pathogenic	-1.082	Destabilizing	0.934	D	0.504	neutral	N	0.508090544	None	None	I
I/P	0.9906	likely_pathogenic	0.993	pathogenic	-1.229	Destabilizing	0.974	D	0.519	neutral	None	None	None	None	I
I/Q	0.8806	likely_pathogenic	0.8917	pathogenic	-1.291	Destabilizing	0.974	D	0.512	neutral	None	None	None	None	I
I/R	0.8805	likely_pathogenic	0.8874	pathogenic	-0.689	Destabilizing	0.949	D	0.511	neutral	None	None	None	None	I
I/S	0.7376	likely_pathogenic	0.7753	pathogenic	-1.616	Destabilizing	0.669	D	0.433	neutral	N	0.474423849	None	None	I
I/T	0.464	ambiguous	0.48	ambiguous	-1.517	Destabilizing	0.005	N	0.164	neutral	N	0.448188777	None	None	I
I/V	0.1971	likely_benign	0.2057	benign	-1.229	Destabilizing	0.022	N	0.121	neutral	N	0.486242649	None	None	I
I/W	0.9341	likely_pathogenic	0.9301	pathogenic	-1.385	Destabilizing	0.998	D	0.506	neutral	None	None	None	None	I
I/Y	0.819	likely_pathogenic	0.8492	pathogenic	-1.203	Destabilizing	0.974	D	0.456	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.