TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24896	74911;74912;74913	chr2:178571446;178571445;178571444	chr2:179436173;179436172;179436171
N2AB	23255	69988;69989;69990	chr2:178571446;178571445;178571444	chr2:179436173;179436172;179436171
N2A	22328	67207;67208;67209	chr2:178571446;178571445;178571444	chr2:179436173;179436172;179436171
N2B	15831	47716;47717;47718	chr2:178571446;178571445;178571444	chr2:179436173;179436172;179436171
Novex-1	15956	48091;48092;48093	chr2:178571446;178571445;178571444	chr2:179436173;179436172;179436171
Novex-2	16023	48292;48293;48294	chr2:178571446;178571445;178571444	chr2:179436173;179436172;179436171
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-68
• Domain position: 89
• Structural Position: 122
• Q(SASA): 0.9274
• 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
N/S	None	None	0.001	N	0.187	0.153	0.0551355673512	gnomAD-4.0.0	3.42164E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.5983E-06	1.15942E-05	0
N/T	rs1708142554	None	None	N	0.059	0.181	0.0920862733494	gnomAD-4.0.0	2.73731E-06	None	None	None	None	N	None	0	0	None	0	7.57308E-05	None	0	0	8.99575E-07	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
N/A	0.1291	likely_benign	0.1337	benign	-0.853	Destabilizing	0.002	N	0.186	neutral	None	None	None	None	N
N/C	0.1509	likely_benign	0.1543	benign	0.018	Stabilizing	0.131	N	0.371	neutral	None	None	None	None	N
N/D	0.12	likely_benign	0.1258	benign	0.106	Stabilizing	None	N	0.051	neutral	N	0.399142549	None	None	N
N/E	0.2402	likely_benign	0.2593	benign	0.195	Stabilizing	0.004	N	0.198	neutral	None	None	None	None	N
N/F	0.29	likely_benign	0.3092	benign	-0.735	Destabilizing	0.021	N	0.583	neutral	None	None	None	None	N
N/G	0.2405	likely_benign	0.2472	benign	-1.164	Destabilizing	0.009	N	0.198	neutral	None	None	None	None	N
N/H	0.1036	likely_benign	0.1093	benign	-0.732	Destabilizing	0.257	N	0.353	neutral	N	0.484838736	None	None	N
N/I	0.084	likely_benign	0.0844	benign	-0.072	Destabilizing	0.003	N	0.225	neutral	N	0.46023108	None	None	N
N/K	0.2821	likely_benign	0.3009	benign	0.066	Stabilizing	0.007	N	0.202	neutral	N	0.437660864	None	None	N
N/L	0.0958	likely_benign	0.0979	benign	-0.072	Destabilizing	None	N	0.213	neutral	None	None	None	None	N
N/M	0.1528	likely_benign	0.1616	benign	0.199	Stabilizing	None	N	0.249	neutral	None	None	None	None	N
N/P	0.2251	likely_benign	0.2488	benign	-0.303	Destabilizing	0.041	N	0.511	neutral	None	None	None	None	N
N/Q	0.2323	likely_benign	0.2502	benign	-0.496	Destabilizing	0.041	N	0.311	neutral	None	None	None	None	N
N/R	0.3205	likely_benign	0.3439	ambiguous	0.084	Stabilizing	0.021	N	0.304	neutral	None	None	None	None	N
N/S	0.0706	likely_benign	0.0711	benign	-0.651	Destabilizing	0.001	N	0.187	neutral	N	0.476043107	None	None	N
N/T	0.0647	likely_benign	0.0653	benign	-0.357	Destabilizing	None	N	0.059	neutral	N	0.390715066	None	None	N
N/V	0.0871	likely_benign	0.0881	benign	-0.303	Destabilizing	None	N	0.271	neutral	None	None	None	None	N
N/W	0.5951	likely_pathogenic	0.6177	pathogenic	-0.484	Destabilizing	0.633	D	0.356	neutral	None	None	None	None	N
N/Y	0.1227	likely_benign	0.1265	benign	-0.264	Destabilizing	0.102	N	0.569	neutral	D	0.522183616	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.