TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16340	49243;49244;49245	chr2:178614496;178614495;178614494	chr2:179479223;179479222;179479221
N2AB	14699	44320;44321;44322	chr2:178614496;178614495;178614494	chr2:179479223;179479222;179479221
N2A	13772	41539;41540;41541	chr2:178614496;178614495;178614494	chr2:179479223;179479222;179479221
N2B	7275	22048;22049;22050	chr2:178614496;178614495;178614494	chr2:179479223;179479222;179479221
Novex-1	7400	22423;22424;22425	chr2:178614496;178614495;178614494	chr2:179479223;179479222;179479221
Novex-2	7467	22624;22625;22626	chr2:178614496;178614495;178614494	chr2:179479223;179479222;179479221
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Ig-110
• Domain position: 79
• Structural Position: 166
• Q(SASA): 0.4354
• 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
A/T	rs1465666542	-0.37	1.0	N	0.716	0.465	0.651728555758	gnomAD-2.1.1	4.06E-06	None	None	None	None	I	None	0	0	None	1.00827E-04	0	None	0	None	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
A/C	0.808	likely_pathogenic	0.8033	pathogenic	-0.79	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	I
A/D	0.8441	likely_pathogenic	0.8433	pathogenic	-0.778	Destabilizing	1.0	D	0.779	deleterious	N	0.506645147	None	None	I
A/E	0.8332	likely_pathogenic	0.8415	pathogenic	-0.926	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	I
A/F	0.9005	likely_pathogenic	0.9063	pathogenic	-0.914	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	I
A/G	0.4814	ambiguous	0.4806	ambiguous	-0.405	Destabilizing	1.0	D	0.603	neutral	D	0.646423626	None	None	I
A/H	0.9074	likely_pathogenic	0.9061	pathogenic	-0.441	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	I
A/I	0.8409	likely_pathogenic	0.8737	pathogenic	-0.372	Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	I
A/K	0.8698	likely_pathogenic	0.8712	pathogenic	-0.838	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	I
A/L	0.79	likely_pathogenic	0.8023	pathogenic	-0.372	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	I
A/M	0.7368	likely_pathogenic	0.7674	pathogenic	-0.457	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	I
A/N	0.7884	likely_pathogenic	0.7854	pathogenic	-0.483	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	I
A/P	0.9975	likely_pathogenic	0.9973	pathogenic	-0.329	Destabilizing	1.0	D	0.757	deleterious	D	0.646533746	None	None	I
A/Q	0.7438	likely_pathogenic	0.736	pathogenic	-0.778	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	I
A/R	0.8463	likely_pathogenic	0.8385	pathogenic	-0.318	Destabilizing	1.0	D	0.76	deleterious	None	None	None	None	I
A/S	0.2243	likely_benign	0.2372	benign	-0.639	Destabilizing	1.0	D	0.607	neutral	N	0.507439841	None	None	I
A/T	0.3093	likely_benign	0.3674	ambiguous	-0.715	Destabilizing	1.0	D	0.716	prob.delet.	N	0.506785419	None	None	I
A/V	0.5289	ambiguous	0.5894	pathogenic	-0.329	Destabilizing	1.0	D	0.677	prob.neutral	N	0.508438044	None	None	I
A/W	0.9883	likely_pathogenic	0.9889	pathogenic	-1.066	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	I
A/Y	0.9385	likely_pathogenic	0.9419	pathogenic	-0.73	Destabilizing	1.0	D	0.779	deleterious	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.