TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29449	88570;88571;88572	chr2:178555114;178555113;178555112	chr2:179419841;179419840;179419839
N2AB	27808	83647;83648;83649	chr2:178555114;178555113;178555112	chr2:179419841;179419840;179419839
N2A	26881	80866;80867;80868	chr2:178555114;178555113;178555112	chr2:179419841;179419840;179419839
N2B	20384	61375;61376;61377	chr2:178555114;178555113;178555112	chr2:179419841;179419840;179419839
Novex-1	20509	61750;61751;61752	chr2:178555114;178555113;178555112	chr2:179419841;179419840;179419839
Novex-2	20576	61951;61952;61953	chr2:178555114;178555113;178555112	chr2:179419841;179419840;179419839
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: Ig-146
• Domain position: 6
• Structural Position: 11
• Q(SASA): 0.3771
• 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/F	None	None	0.97	N	0.471	0.321	0.518641613453	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	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
V/A	0.1523	likely_benign	0.1261	benign	-1.013	Destabilizing	0.489	N	0.434	neutral	N	0.443489893	None	None	N
V/C	0.7711	likely_pathogenic	0.7121	pathogenic	-0.795	Destabilizing	0.998	D	0.513	neutral	None	None	None	None	N
V/D	0.3309	likely_benign	0.2663	benign	-0.668	Destabilizing	0.698	D	0.506	neutral	N	0.35500133	None	None	N
V/E	0.2789	likely_benign	0.2371	benign	-0.744	Destabilizing	0.076	N	0.325	neutral	None	None	None	None	N
V/F	0.2287	likely_benign	0.1774	benign	-0.922	Destabilizing	0.97	D	0.471	neutral	N	0.473639441	None	None	N
V/G	0.2479	likely_benign	0.2061	benign	-1.228	Destabilizing	0.822	D	0.509	neutral	N	0.429405875	None	None	N
V/H	0.6738	likely_pathogenic	0.5801	pathogenic	-0.694	Destabilizing	0.998	D	0.608	neutral	None	None	None	None	N
V/I	0.0811	likely_benign	0.0746	benign	-0.569	Destabilizing	0.822	D	0.452	neutral	N	0.454784322	None	None	N
V/K	0.4358	ambiguous	0.3525	ambiguous	-0.875	Destabilizing	0.86	D	0.477	neutral	None	None	None	None	N
V/L	0.2539	likely_benign	0.2035	benign	-0.569	Destabilizing	0.489	N	0.467	neutral	N	0.462249012	None	None	N
V/M	0.1406	likely_benign	0.1163	benign	-0.487	Destabilizing	0.978	D	0.441	neutral	None	None	None	None	N
V/N	0.289	likely_benign	0.219	benign	-0.584	Destabilizing	0.956	D	0.571	neutral	None	None	None	None	N
V/P	0.5438	ambiguous	0.446	ambiguous	-0.681	Destabilizing	0.978	D	0.538	neutral	None	None	None	None	N
V/Q	0.4327	ambiguous	0.3563	ambiguous	-0.834	Destabilizing	0.956	D	0.537	neutral	None	None	None	None	N
V/R	0.4588	ambiguous	0.3576	ambiguous	-0.291	Destabilizing	0.956	D	0.585	neutral	None	None	None	None	N
V/S	0.2465	likely_benign	0.1937	benign	-1.034	Destabilizing	0.754	D	0.48	neutral	None	None	None	None	N
V/T	0.133	likely_benign	0.1137	benign	-1.009	Destabilizing	0.019	N	0.274	neutral	None	None	None	None	N
V/W	0.8177	likely_pathogenic	0.7405	pathogenic	-0.993	Destabilizing	0.998	D	0.669	neutral	None	None	None	None	N
V/Y	0.5616	ambiguous	0.4822	ambiguous	-0.732	Destabilizing	0.993	D	0.477	neutral	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.