TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27232	81919;81920;81921	chr2:178564438;178564437;178564436	chr2:179429165;179429164;179429163
N2AB	25591	76996;76997;76998	chr2:178564438;178564437;178564436	chr2:179429165;179429164;179429163
N2A	24664	74215;74216;74217	chr2:178564438;178564437;178564436	chr2:179429165;179429164;179429163
N2B	18167	54724;54725;54726	chr2:178564438;178564437;178564436	chr2:179429165;179429164;179429163
Novex-1	18292	55099;55100;55101	chr2:178564438;178564437;178564436	chr2:179429165;179429164;179429163
Novex-2	18359	55300;55301;55302	chr2:178564438;178564437;178564436	chr2:179429165;179429164;179429163
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: Fn3-86
• Domain position: 63
• Structural Position: 93
• Q(SASA): 0.1364
• 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	0.978	N	0.679	0.406	0.608695890411	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.9375E-06	0	0
V/M	rs2154162679	None	0.994	D	0.693	0.374	0.605774515499	gnomAD-4.0.0	1.59378E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86193E-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	0.4875	ambiguous	0.3253	benign	-1.629	Destabilizing	0.978	D	0.679	prob.neutral	N	0.474213757	None	None	N
V/C	0.9044	likely_pathogenic	0.8615	pathogenic	-1.337	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
V/D	0.9939	likely_pathogenic	0.9845	pathogenic	-1.873	Destabilizing	0.999	D	0.836	deleterious	None	None	None	None	N
V/E	0.9811	likely_pathogenic	0.9631	pathogenic	-1.606	Destabilizing	0.999	D	0.801	deleterious	D	0.555949621	None	None	N
V/F	0.8355	likely_pathogenic	0.7368	pathogenic	-0.95	Destabilizing	0.995	D	0.748	deleterious	None	None	None	None	N
V/G	0.9254	likely_pathogenic	0.8424	pathogenic	-2.216	Highly Destabilizing	0.999	D	0.838	deleterious	D	0.555949621	None	None	N
V/H	0.9937	likely_pathogenic	0.9865	pathogenic	-2.128	Highly Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
V/I	0.1028	likely_benign	0.0967	benign	0.018	Stabilizing	0.437	N	0.197	neutral	None	None	None	None	N
V/K	0.9907	likely_pathogenic	0.9821	pathogenic	-1.164	Destabilizing	0.999	D	0.807	deleterious	None	None	None	None	N
V/L	0.6333	likely_pathogenic	0.5285	ambiguous	0.018	Stabilizing	0.121	N	0.327	neutral	N	0.472467967	None	None	N
V/M	0.6427	likely_pathogenic	0.5173	ambiguous	-0.224	Destabilizing	0.994	D	0.693	prob.neutral	D	0.525817497	None	None	N
V/N	0.9782	likely_pathogenic	0.9461	pathogenic	-1.593	Destabilizing	0.999	D	0.851	deleterious	None	None	None	None	N
V/P	0.9867	likely_pathogenic	0.9731	pathogenic	-0.503	Destabilizing	0.999	D	0.791	deleterious	None	None	None	None	N
V/Q	0.9798	likely_pathogenic	0.9607	pathogenic	-1.298	Destabilizing	0.999	D	0.818	deleterious	None	None	None	None	N
V/R	0.9834	likely_pathogenic	0.9697	pathogenic	-1.331	Destabilizing	0.999	D	0.848	deleterious	None	None	None	None	N
V/S	0.8693	likely_pathogenic	0.7241	pathogenic	-2.284	Highly Destabilizing	0.999	D	0.809	deleterious	None	None	None	None	N
V/T	0.7452	likely_pathogenic	0.5386	ambiguous	-1.838	Destabilizing	0.992	D	0.668	neutral	None	None	None	None	N
V/W	0.9976	likely_pathogenic	0.9951	pathogenic	-1.438	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
V/Y	0.9834	likely_pathogenic	0.9692	pathogenic	-0.981	Destabilizing	0.999	D	0.723	prob.delet.	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.