TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29567	88924;88925;88926	chr2:178554648;178554647;178554646	chr2:179419375;179419374;179419373
N2AB	27926	84001;84002;84003	chr2:178554648;178554647;178554646	chr2:179419375;179419374;179419373
N2A	26999	81220;81221;81222	chr2:178554648;178554647;178554646	chr2:179419375;179419374;179419373
N2B	20502	61729;61730;61731	chr2:178554648;178554647;178554646	chr2:179419375;179419374;179419373
Novex-1	20627	62104;62105;62106	chr2:178554648;178554647;178554646	chr2:179419375;179419374;179419373
Novex-2	20694	62305;62306;62307	chr2:178554648;178554647;178554646	chr2:179419375;179419374;179419373
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-103
• Domain position: 35
• Structural Position: 36
• Q(SASA): 0.3682
• 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/N	None	None	1.0	N	0.788	0.435	0.442160178816	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05

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	0.1958	likely_benign	0.1901	benign	-0.838	Destabilizing	0.999	D	0.544	neutral	N	0.514658094	None	None	N
T/C	0.6329	likely_pathogenic	0.6231	pathogenic	-0.321	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
T/D	0.5164	ambiguous	0.5061	ambiguous	-0.732	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
T/E	0.5373	ambiguous	0.4939	ambiguous	-0.692	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
T/F	0.5663	likely_pathogenic	0.56	ambiguous	-0.612	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
T/G	0.3764	ambiguous	0.4055	ambiguous	-1.151	Destabilizing	1.0	D	0.712	prob.delet.	None	None	None	None	N
T/H	0.498	ambiguous	0.5008	ambiguous	-1.467	Destabilizing	1.0	D	0.722	prob.delet.	None	None	None	None	N
T/I	0.4684	ambiguous	0.4113	ambiguous	-0.071	Destabilizing	1.0	D	0.775	deleterious	N	0.469575267	None	None	N
T/K	0.5105	ambiguous	0.4692	ambiguous	-1.048	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
T/L	0.2173	likely_benign	0.1972	benign	-0.071	Destabilizing	0.999	D	0.683	prob.neutral	None	None	None	None	N
T/M	0.1738	likely_benign	0.1636	benign	0.218	Stabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
T/N	0.2169	likely_benign	0.2135	benign	-0.985	Destabilizing	1.0	D	0.788	deleterious	N	0.490477452	None	None	N
T/P	0.6666	likely_pathogenic	0.6913	pathogenic	-0.295	Destabilizing	1.0	D	0.757	deleterious	D	0.527788826	None	None	N
T/Q	0.4291	ambiguous	0.4211	ambiguous	-1.022	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
T/R	0.4757	ambiguous	0.4512	ambiguous	-0.905	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
T/S	0.1054	likely_benign	0.1165	benign	-1.155	Destabilizing	0.999	D	0.542	neutral	N	0.516750792	None	None	N
T/V	0.3912	ambiguous	0.3466	ambiguous	-0.295	Destabilizing	0.999	D	0.631	neutral	None	None	None	None	N
T/W	0.8572	likely_pathogenic	0.8595	pathogenic	-0.669	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
T/Y	0.6096	likely_pathogenic	0.6016	pathogenic	-0.466	Destabilizing	1.0	D	0.773	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.