TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27438	82537;82538;82539	chr2:178563820;178563819;178563818	chr2:179428547;179428546;179428545
N2AB	25797	77614;77615;77616	chr2:178563820;178563819;178563818	chr2:179428547;179428546;179428545
N2A	24870	74833;74834;74835	chr2:178563820;178563819;178563818	chr2:179428547;179428546;179428545
N2B	18373	55342;55343;55344	chr2:178563820;178563819;178563818	chr2:179428547;179428546;179428545
Novex-1	18498	55717;55718;55719	chr2:178563820;178563819;178563818	chr2:179428547;179428546;179428545
Novex-2	18565	55918;55919;55920	chr2:178563820;178563819;178563818	chr2:179428547;179428546;179428545
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: Fn3-87
• Domain position: 70
• Structural Position: 102
• Q(SASA): 0.3304
• 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/D	rs2154161681	None	0.958	N	0.504	0.288	0.247322355667	gnomAD-4.0.0	1.59138E-06	None	None	None	None	N	None	0	0	None	0	2.77546E-05	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
N/A	0.7895	likely_pathogenic	0.8158	pathogenic	-1.02	Destabilizing	0.968	D	0.595	neutral	None	None	None	None	N
N/C	0.5704	likely_pathogenic	0.5795	pathogenic	-0.065	Destabilizing	1.0	D	0.728	prob.delet.	None	None	None	None	N
N/D	0.716	likely_pathogenic	0.7858	pathogenic	-0.751	Destabilizing	0.958	D	0.504	neutral	N	0.468886796	None	None	N
N/E	0.9055	likely_pathogenic	0.9253	pathogenic	-0.642	Destabilizing	0.968	D	0.557	neutral	None	None	None	None	N
N/F	0.9287	likely_pathogenic	0.9372	pathogenic	-0.751	Destabilizing	0.995	D	0.74	deleterious	None	None	None	None	N
N/G	0.7358	likely_pathogenic	0.7531	pathogenic	-1.374	Destabilizing	0.968	D	0.421	neutral	None	None	None	None	N
N/H	0.3492	ambiguous	0.3827	ambiguous	-1.051	Destabilizing	0.142	N	0.281	neutral	N	0.447234779	None	None	N
N/I	0.792	likely_pathogenic	0.7942	pathogenic	-0.11	Destabilizing	0.994	D	0.739	prob.delet.	N	0.468886796	None	None	N
N/K	0.8792	likely_pathogenic	0.9018	pathogenic	-0.342	Destabilizing	0.958	D	0.576	neutral	N	0.451677807	None	None	N
N/L	0.7377	likely_pathogenic	0.7538	pathogenic	-0.11	Destabilizing	0.991	D	0.727	prob.delet.	None	None	None	None	N
N/M	0.8024	likely_pathogenic	0.8067	pathogenic	0.412	Stabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	N
N/P	0.9786	likely_pathogenic	0.9778	pathogenic	-0.383	Destabilizing	0.998	D	0.698	prob.neutral	None	None	None	None	N
N/Q	0.8292	likely_pathogenic	0.8491	pathogenic	-0.981	Destabilizing	0.991	D	0.678	prob.neutral	None	None	None	None	N
N/R	0.8318	likely_pathogenic	0.8603	pathogenic	-0.342	Destabilizing	0.991	D	0.676	prob.neutral	None	None	None	None	N
N/S	0.2698	likely_benign	0.2873	benign	-1.035	Destabilizing	0.958	D	0.438	neutral	N	0.457448986	None	None	N
N/T	0.6471	likely_pathogenic	0.6711	pathogenic	-0.728	Destabilizing	0.979	D	0.574	neutral	N	0.419674458	None	None	N
N/V	0.7541	likely_pathogenic	0.7632	pathogenic	-0.383	Destabilizing	0.995	D	0.717	prob.delet.	None	None	None	None	N
N/W	0.9699	likely_pathogenic	0.9732	pathogenic	-0.495	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
N/Y	0.6132	likely_pathogenic	0.6294	pathogenic	-0.297	Destabilizing	0.976	D	0.687	prob.neutral	N	0.492106386	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.