TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15853	47782;47783;47784	chr2:178617794;178617793;178617792	chr2:179482521;179482520;179482519
N2AB	14212	42859;42860;42861	chr2:178617794;178617793;178617792	chr2:179482521;179482520;179482519
N2A	13285	40078;40079;40080	chr2:178617794;178617793;178617792	chr2:179482521;179482520;179482519
N2B	6788	20587;20588;20589	chr2:178617794;178617793;178617792	chr2:179482521;179482520;179482519
Novex-1	6913	20962;20963;20964	chr2:178617794;178617793;178617792	chr2:179482521;179482520;179482519
Novex-2	6980	21163;21164;21165	chr2:178617794;178617793;178617792	chr2:179482521;179482520;179482519
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-2
• Domain position: 96
• Structural Position: 130
• Q(SASA): 0.0629
• 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
V/A	None	None	0.622	N	0.534	0.249	0.335661160332	gnomAD-4.0.0	1.59448E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86428E-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
V/A	0.5091	ambiguous	0.436	ambiguous	-2.418	Highly Destabilizing	0.622	D	0.534	neutral	N	0.389318841	None	None	N
V/C	0.9268	likely_pathogenic	0.9256	pathogenic	-2.144	Highly Destabilizing	0.998	D	0.699	prob.delet.	None	None	None	None	N
V/D	0.9903	likely_pathogenic	0.9893	pathogenic	-3.26	Highly Destabilizing	0.989	D	0.797	deleterious	N	0.47711675	None	None	N
V/E	0.9777	likely_pathogenic	0.976	pathogenic	-3.039	Highly Destabilizing	0.991	D	0.707	prob.delet.	None	None	None	None	N
V/F	0.7842	likely_pathogenic	0.7588	pathogenic	-1.327	Destabilizing	0.933	D	0.727	deleterious	N	0.453866942	None	None	N
V/G	0.8211	likely_pathogenic	0.8063	pathogenic	-2.926	Highly Destabilizing	0.989	D	0.722	deleterious	N	0.459858577	None	None	N
V/H	0.9935	likely_pathogenic	0.9927	pathogenic	-2.51	Highly Destabilizing	0.998	D	0.799	deleterious	None	None	None	None	N
V/I	0.1067	likely_benign	0.1022	benign	-0.982	Destabilizing	0.002	N	0.107	neutral	N	0.382427813	None	None	N
V/K	0.9854	likely_pathogenic	0.9816	pathogenic	-1.949	Destabilizing	0.974	D	0.71	prob.delet.	None	None	None	None	N
V/L	0.5445	ambiguous	0.5051	ambiguous	-0.982	Destabilizing	0.264	N	0.305	neutral	N	0.444117001	None	None	N
V/M	0.6078	likely_pathogenic	0.5779	pathogenic	-1.281	Destabilizing	0.949	D	0.686	prob.delet.	None	None	None	None	N
V/N	0.9641	likely_pathogenic	0.9602	pathogenic	-2.343	Highly Destabilizing	0.991	D	0.79	deleterious	None	None	None	None	N
V/P	0.8599	likely_pathogenic	0.8376	pathogenic	-1.438	Destabilizing	0.991	D	0.767	deleterious	None	None	None	None	N
V/Q	0.9796	likely_pathogenic	0.9757	pathogenic	-2.189	Highly Destabilizing	0.991	D	0.753	deleterious	None	None	None	None	N
V/R	0.972	likely_pathogenic	0.9661	pathogenic	-1.73	Destabilizing	0.991	D	0.789	deleterious	None	None	None	None	N
V/S	0.8759	likely_pathogenic	0.8532	pathogenic	-2.906	Highly Destabilizing	0.974	D	0.703	prob.delet.	None	None	None	None	N
V/T	0.7193	likely_pathogenic	0.6786	pathogenic	-2.555	Highly Destabilizing	0.841	D	0.62	neutral	None	None	None	None	N
V/W	0.9954	likely_pathogenic	0.9944	pathogenic	-1.812	Destabilizing	0.998	D	0.788	deleterious	None	None	None	None	N
V/Y	0.9803	likely_pathogenic	0.9753	pathogenic	-1.536	Destabilizing	0.991	D	0.757	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.