TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2262	7009;7010;7011	chr2:178774927;178774926;178774925	chr2:179639654;179639653;179639652
N2AB	2262	7009;7010;7011	chr2:178774927;178774926;178774925	chr2:179639654;179639653;179639652
N2A	2262	7009;7010;7011	chr2:178774927;178774926;178774925	chr2:179639654;179639653;179639652
N2B	2216	6871;6872;6873	chr2:178774927;178774926;178774925	chr2:179639654;179639653;179639652
Novex-1	2216	6871;6872;6873	chr2:178774927;178774926;178774925	chr2:179639654;179639653;179639652
Novex-2	2216	6871;6872;6873	chr2:178774927;178774926;178774925	chr2:179639654;179639653;179639652
Novex-3	2262	7009;7010;7011	chr2:178774927;178774926;178774925	chr2:179639654;179639653;179639652

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-11
• Domain position: 89
• Structural Position: 177
• Q(SASA): 0.8774
• 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/I	rs1430183288	-0.085	0.997	D	0.723	0.526	0.700794567812	gnomAD-2.1.1	3.99E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.85E-06	0
V/I	rs1430183288	-0.085	0.997	D	0.723	0.526	0.700794567812	gnomAD-4.0.0	1.59173E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85783E-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	0.6015	likely_pathogenic	0.5701	pathogenic	-1.666	Destabilizing	0.999	D	0.758	deleterious	D	0.757021101	None	None	N
V/C	0.9506	likely_pathogenic	0.9404	pathogenic	-1.132	Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
V/D	0.9833	likely_pathogenic	0.9828	pathogenic	-1.606	Destabilizing	1.0	D	0.806	deleterious	D	0.756300027	None	None	N
V/E	0.9503	likely_pathogenic	0.948	pathogenic	-1.581	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
V/F	0.811	likely_pathogenic	0.7801	pathogenic	-1.202	Destabilizing	1.0	D	0.837	deleterious	D	0.757021101	None	None	N
V/G	0.8259	likely_pathogenic	0.8127	pathogenic	-2.008	Highly Destabilizing	1.0	D	0.765	deleterious	D	0.756300027	None	None	N
V/H	0.9857	likely_pathogenic	0.9829	pathogenic	-1.569	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
V/I	0.1219	likely_benign	0.1082	benign	-0.806	Destabilizing	0.997	D	0.723	prob.delet.	D	0.592638176	None	None	N
V/K	0.9348	likely_pathogenic	0.9332	pathogenic	-1.387	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
V/L	0.6413	likely_pathogenic	0.5812	pathogenic	-0.806	Destabilizing	0.997	D	0.759	deleterious	D	0.722562219	None	None	N
V/M	0.6053	likely_pathogenic	0.5419	ambiguous	-0.679	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
V/N	0.9451	likely_pathogenic	0.9417	pathogenic	-1.204	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
V/P	0.9386	likely_pathogenic	0.9344	pathogenic	-1.06	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
V/Q	0.948	likely_pathogenic	0.9419	pathogenic	-1.356	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
V/R	0.9083	likely_pathogenic	0.9073	pathogenic	-0.907	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
V/S	0.8179	likely_pathogenic	0.8052	pathogenic	-1.737	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
V/T	0.5251	ambiguous	0.5135	ambiguous	-1.608	Destabilizing	0.999	D	0.795	deleterious	None	None	None	None	N
V/W	0.9946	likely_pathogenic	0.9923	pathogenic	-1.419	Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	N
V/Y	0.9765	likely_pathogenic	0.9725	pathogenic	-1.135	Destabilizing	1.0	D	0.843	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.