TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16711	50356;50357;50358	chr2:178612394;178612393;178612392	chr2:179477121;179477120;179477119
N2AB	15070	45433;45434;45435	chr2:178612394;178612393;178612392	chr2:179477121;179477120;179477119
N2A	14143	42652;42653;42654	chr2:178612394;178612393;178612392	chr2:179477121;179477120;179477119
N2B	7646	23161;23162;23163	chr2:178612394;178612393;178612392	chr2:179477121;179477120;179477119
Novex-1	7771	23536;23537;23538	chr2:178612394;178612393;178612392	chr2:179477121;179477120;179477119
Novex-2	7838	23737;23738;23739	chr2:178612394;178612393;178612392	chr2:179477121;179477120;179477119
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-9
• Domain position: 61
• Structural Position: 92
• Q(SASA): 0.3404
• 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
T/R	None	None	0.993	N	0.797	0.443	0.594705806306	gnomAD-4.0.0	1.59393E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8622E-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
T/A	0.1116	likely_benign	0.1056	benign	-0.523	Destabilizing	0.898	D	0.48	neutral	D	0.557935098	None	None	N
T/C	0.5294	ambiguous	0.5278	ambiguous	-0.226	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
T/D	0.7971	likely_pathogenic	0.7743	pathogenic	-0.073	Destabilizing	0.995	D	0.727	prob.delet.	None	None	None	None	N
T/E	0.6764	likely_pathogenic	0.6172	pathogenic	-0.141	Destabilizing	0.995	D	0.717	prob.delet.	None	None	None	None	N
T/F	0.4874	ambiguous	0.4744	ambiguous	-0.927	Destabilizing	0.999	D	0.841	deleterious	None	None	None	None	N
T/G	0.4678	ambiguous	0.4554	ambiguous	-0.686	Destabilizing	0.966	D	0.65	neutral	None	None	None	None	N
T/H	0.4947	ambiguous	0.4511	ambiguous	-1.038	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
T/I	0.2272	likely_benign	0.2097	benign	-0.206	Destabilizing	0.997	D	0.791	deleterious	N	0.483812706	None	None	N
T/K	0.5269	ambiguous	0.4647	ambiguous	-0.516	Destabilizing	0.993	D	0.727	prob.delet.	N	0.483389441	None	None	N
T/L	0.1723	likely_benign	0.1715	benign	-0.206	Destabilizing	0.983	D	0.619	neutral	None	None	None	None	N
T/M	0.1396	likely_benign	0.1305	benign	0.135	Stabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
T/N	0.2249	likely_benign	0.2078	benign	-0.274	Destabilizing	0.995	D	0.641	neutral	None	None	None	None	N
T/P	0.2911	likely_benign	0.3374	benign	-0.282	Destabilizing	0.997	D	0.797	deleterious	D	0.578766908	None	None	N
T/Q	0.396	ambiguous	0.3458	ambiguous	-0.54	Destabilizing	0.998	D	0.81	deleterious	None	None	None	None	N
T/R	0.4856	ambiguous	0.4311	ambiguous	-0.21	Destabilizing	0.993	D	0.797	deleterious	N	0.488346276	None	None	N
T/S	0.1496	likely_benign	0.1415	benign	-0.487	Destabilizing	0.362	N	0.316	neutral	D	0.52288301	None	None	N
T/V	0.1463	likely_benign	0.1453	benign	-0.282	Destabilizing	0.983	D	0.525	neutral	None	None	None	None	N
T/W	0.8723	likely_pathogenic	0.8711	pathogenic	-0.895	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
T/Y	0.634	likely_pathogenic	0.6151	pathogenic	-0.639	Destabilizing	0.999	D	0.841	deleterious	None	None	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.