TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17074	51445;51446;51447	chr2:178610306;178610305;178610304	chr2:179475033;179475032;179475031
N2AB	15433	46522;46523;46524	chr2:178610306;178610305;178610304	chr2:179475033;179475032;179475031
N2A	14506	43741;43742;43743	chr2:178610306;178610305;178610304	chr2:179475033;179475032;179475031
N2B	8009	24250;24251;24252	chr2:178610306;178610305;178610304	chr2:179475033;179475032;179475031
Novex-1	8134	24625;24626;24627	chr2:178610306;178610305;178610304	chr2:179475033;179475032;179475031
Novex-2	8201	24826;24827;24828	chr2:178610306;178610305;178610304	chr2:179475033;179475032;179475031
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-12
• Domain position: 28
• Structural Position: 30
• Q(SASA): 0.3271
• 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
D/V	rs1553693510	None	1.0	D	0.703	0.609	0.602933245068	gnomAD-4.0.0	1.20033E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.31251E-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
D/A	0.8969	likely_pathogenic	0.8991	pathogenic	-0.79	Destabilizing	1.0	D	0.724	prob.delet.	D	0.529999741	None	None	I
D/C	0.9772	likely_pathogenic	0.9795	pathogenic	-0.33	Destabilizing	1.0	D	0.655	neutral	None	None	None	None	I
D/E	0.8368	likely_pathogenic	0.8541	pathogenic	-0.635	Destabilizing	1.0	D	0.449	neutral	D	0.550873208	None	None	I
D/F	0.99	likely_pathogenic	0.9903	pathogenic	-0.433	Destabilizing	1.0	D	0.647	neutral	None	None	None	None	I
D/G	0.8921	likely_pathogenic	0.9001	pathogenic	-1.155	Destabilizing	1.0	D	0.717	prob.delet.	D	0.630077015	None	None	I
D/H	0.9325	likely_pathogenic	0.9337	pathogenic	-0.815	Destabilizing	1.0	D	0.657	neutral	D	0.623366979	None	None	I
D/I	0.9766	likely_pathogenic	0.978	pathogenic	0.185	Stabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	I
D/K	0.9778	likely_pathogenic	0.9783	pathogenic	-0.569	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	I
D/L	0.962	likely_pathogenic	0.9627	pathogenic	0.185	Stabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	I
D/M	0.992	likely_pathogenic	0.9918	pathogenic	0.727	Stabilizing	1.0	D	0.646	neutral	None	None	None	None	I
D/N	0.3729	ambiguous	0.3764	ambiguous	-0.964	Destabilizing	1.0	D	0.716	prob.delet.	N	0.51837913	None	None	I
D/P	0.9762	likely_pathogenic	0.9742	pathogenic	-0.116	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	I
D/Q	0.964	likely_pathogenic	0.9637	pathogenic	-0.805	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	I
D/R	0.9731	likely_pathogenic	0.9732	pathogenic	-0.465	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	I
D/S	0.6378	likely_pathogenic	0.6448	pathogenic	-1.287	Destabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	I
D/T	0.8773	likely_pathogenic	0.8784	pathogenic	-0.981	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	I
D/V	0.9393	likely_pathogenic	0.943	pathogenic	-0.116	Destabilizing	1.0	D	0.703	prob.neutral	D	0.636115234	None	None	I
D/W	0.9977	likely_pathogenic	0.9977	pathogenic	-0.254	Destabilizing	1.0	D	0.651	neutral	None	None	None	None	I
D/Y	0.9273	likely_pathogenic	0.9328	pathogenic	-0.196	Destabilizing	1.0	D	0.63	neutral	D	0.743028773	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.