TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22267	67024;67025;67026	chr2:178580580;178580579;178580578	chr2:179445307;179445306;179445305
N2AB	20626	62101;62102;62103	chr2:178580580;178580579;178580578	chr2:179445307;179445306;179445305
N2A	19699	59320;59321;59322	chr2:178580580;178580579;178580578	chr2:179445307;179445306;179445305
N2B	13202	39829;39830;39831	chr2:178580580;178580579;178580578	chr2:179445307;179445306;179445305
Novex-1	13327	40204;40205;40206	chr2:178580580;178580579;178580578	chr2:179445307;179445306;179445305
Novex-2	13394	40405;40406;40407	chr2:178580580;178580579;178580578	chr2:179445307;179445306;179445305
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTA
• RefSeq wild type template codon: AAT
• Domain: Ig-126
• Domain position: 3
• Structural Position: 3
• Q(SASA): 0.5203
• 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	None	None	0.967	D	0.719	0.233	0.567747928639	gnomAD-4.0.0	6.00161E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	6.56251E-06	0	0
L/V	rs2047467228	None	0.099	N	0.369	0.228	0.260249123532	gnomAD-4.0.0	1.37066E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.80022E-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
L/A	0.8768	likely_pathogenic	0.8455	pathogenic	-1.28	Destabilizing	0.916	D	0.535	neutral	None	None	None	None	I
L/C	0.8806	likely_pathogenic	0.8589	pathogenic	-1.021	Destabilizing	0.999	D	0.711	prob.delet.	None	None	None	None	I
L/D	0.9917	likely_pathogenic	0.9879	pathogenic	-0.467	Destabilizing	0.996	D	0.775	deleterious	None	None	None	None	I
L/E	0.9668	likely_pathogenic	0.9534	pathogenic	-0.461	Destabilizing	0.987	D	0.767	deleterious	None	None	None	None	I
L/F	0.6172	likely_pathogenic	0.5338	ambiguous	-0.808	Destabilizing	0.967	D	0.719	prob.delet.	D	0.531979322	None	None	I
L/G	0.9593	likely_pathogenic	0.9482	pathogenic	-1.583	Destabilizing	0.987	D	0.76	deleterious	None	None	None	None	I
L/H	0.9096	likely_pathogenic	0.8748	pathogenic	-0.734	Destabilizing	0.999	D	0.752	deleterious	None	None	None	None	I
L/I	0.4072	ambiguous	0.3627	ambiguous	-0.535	Destabilizing	0.805	D	0.506	neutral	N	0.480929389	None	None	I
L/K	0.9338	likely_pathogenic	0.9153	pathogenic	-0.886	Destabilizing	0.975	D	0.725	prob.delet.	None	None	None	None	I
L/M	0.2719	likely_benign	0.2301	benign	-0.632	Destabilizing	0.693	D	0.447	neutral	None	None	None	None	I
L/N	0.9448	likely_pathogenic	0.9234	pathogenic	-0.749	Destabilizing	0.987	D	0.779	deleterious	None	None	None	None	I
L/P	0.9926	likely_pathogenic	0.9886	pathogenic	-0.751	Destabilizing	0.996	D	0.778	deleterious	None	None	None	None	I
L/Q	0.8487	likely_pathogenic	0.8013	pathogenic	-0.852	Destabilizing	0.987	D	0.735	prob.delet.	None	None	None	None	I
L/R	0.9057	likely_pathogenic	0.8879	pathogenic	-0.393	Destabilizing	0.987	D	0.735	prob.delet.	None	None	None	None	I
L/S	0.936	likely_pathogenic	0.9107	pathogenic	-1.37	Destabilizing	0.967	D	0.717	prob.delet.	N	0.516430337	None	None	I
L/T	0.8469	likely_pathogenic	0.808	pathogenic	-1.232	Destabilizing	0.975	D	0.636	neutral	None	None	None	None	I
L/V	0.4508	ambiguous	0.4067	ambiguous	-0.751	Destabilizing	0.099	N	0.369	neutral	N	0.502121062	None	None	I
L/W	0.8829	likely_pathogenic	0.8323	pathogenic	-0.844	Destabilizing	0.999	D	0.731	prob.delet.	None	None	None	None	I
L/Y	0.8822	likely_pathogenic	0.8374	pathogenic	-0.626	Destabilizing	0.987	D	0.729	prob.delet.	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.