TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19530	58813;58814;58815	chr2:178593712;178593711;178593710	chr2:179458439;179458438;179458437
N2AB	17889	53890;53891;53892	chr2:178593712;178593711;178593710	chr2:179458439;179458438;179458437
N2A	16962	51109;51110;51111	chr2:178593712;178593711;178593710	chr2:179458439;179458438;179458437
N2B	10465	31618;31619;31620	chr2:178593712;178593711;178593710	chr2:179458439;179458438;179458437
Novex-1	10590	31993;31994;31995	chr2:178593712;178593711;178593710	chr2:179458439;179458438;179458437
Novex-2	10657	32194;32195;32196	chr2:178593712;178593711;178593710	chr2:179458439;179458438;179458437
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Fn3-29
• Domain position: 52
• Structural Position: 68
• Q(SASA): 0.2604
• 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
V/A	rs1187285216	-1.618	0.999	N	0.563	0.389	0.604839314244	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
V/A	rs1187285216	-1.618	0.999	N	0.563	0.389	0.604839314244	gnomAD-4.0.0	3.18425E-06	None	None	None	None	I	None	0	0	None	0	2.78133E-05	None	0	0	0	1.43303E-05	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	0.5517	ambiguous	0.5735	pathogenic	-1.2	Destabilizing	0.999	D	0.563	neutral	N	0.468824344	None	None	I
V/C	0.8917	likely_pathogenic	0.8711	pathogenic	-0.83	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	I
V/D	0.9806	likely_pathogenic	0.9834	pathogenic	-1.075	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	I
V/E	0.9317	likely_pathogenic	0.9455	pathogenic	-1.113	Destabilizing	1.0	D	0.784	deleterious	N	0.502550865	None	None	I
V/F	0.5218	ambiguous	0.56	ambiguous	-1.03	Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	I
V/G	0.8414	likely_pathogenic	0.8619	pathogenic	-1.469	Destabilizing	1.0	D	0.786	deleterious	N	0.507857237	None	None	I
V/H	0.9716	likely_pathogenic	0.9773	pathogenic	-1.025	Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	I
V/I	0.1079	likely_benign	0.1056	benign	-0.584	Destabilizing	0.998	D	0.489	neutral	None	None	None	None	I
V/K	0.9676	likely_pathogenic	0.9759	pathogenic	-1.118	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	I
V/L	0.5612	ambiguous	0.5998	pathogenic	-0.584	Destabilizing	0.997	D	0.543	neutral	N	0.520519029	None	None	I
V/M	0.4403	ambiguous	0.464	ambiguous	-0.458	Destabilizing	1.0	D	0.699	prob.neutral	N	0.494779412	None	None	I
V/N	0.9389	likely_pathogenic	0.9455	pathogenic	-0.855	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	I
V/P	0.9857	likely_pathogenic	0.9884	pathogenic	-0.753	Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	I
V/Q	0.9219	likely_pathogenic	0.9377	pathogenic	-1.049	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	I
V/R	0.9529	likely_pathogenic	0.9611	pathogenic	-0.56	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	I
V/S	0.7985	likely_pathogenic	0.8102	pathogenic	-1.291	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	I
V/T	0.6917	likely_pathogenic	0.7153	pathogenic	-1.22	Destabilizing	0.999	D	0.589	neutral	None	None	None	None	I
V/W	0.9869	likely_pathogenic	0.989	pathogenic	-1.191	Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	I
V/Y	0.9157	likely_pathogenic	0.9267	pathogenic	-0.906	Destabilizing	1.0	D	0.817	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.