TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18490	55693;55694;55695	chr2:178601529;178601528;178601527	chr2:179466256;179466255;179466254
N2AB	16849	50770;50771;50772	chr2:178601529;178601528;178601527	chr2:179466256;179466255;179466254
N2A	15922	47989;47990;47991	chr2:178601529;178601528;178601527	chr2:179466256;179466255;179466254
N2B	9425	28498;28499;28500	chr2:178601529;178601528;178601527	chr2:179466256;179466255;179466254
Novex-1	9550	28873;28874;28875	chr2:178601529;178601528;178601527	chr2:179466256;179466255;179466254
Novex-2	9617	29074;29075;29076	chr2:178601529;178601528;178601527	chr2:179466256;179466255;179466254
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-22
• Domain position: 12
• Structural Position: 14
• Q(SASA): 0.5142
• 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
D/E	None	None	0.067	N	0.247	0.089	0.119812018005	gnomAD-4.0.0	1.59384E-06	None	None	None	None	N	None	0	2.28791E-05	None	0	0	None	0	0	0	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
D/A	0.6055	likely_pathogenic	0.5948	pathogenic	-0.231	Destabilizing	0.988	D	0.661	neutral	N	0.518345516	None	None	N
D/C	0.9247	likely_pathogenic	0.925	pathogenic	0.073	Stabilizing	1.0	D	0.663	neutral	None	None	None	None	N
D/E	0.3499	ambiguous	0.2904	benign	-0.27	Destabilizing	0.067	N	0.247	neutral	N	0.461278725	None	None	N
D/F	0.9362	likely_pathogenic	0.9398	pathogenic	-0.192	Destabilizing	1.0	D	0.678	prob.neutral	None	None	None	None	N
D/G	0.5961	likely_pathogenic	0.577	pathogenic	-0.412	Destabilizing	0.958	D	0.721	prob.delet.	N	0.471711179	None	None	N
D/H	0.7841	likely_pathogenic	0.7638	pathogenic	0.026	Stabilizing	0.998	D	0.682	prob.neutral	N	0.485918322	None	None	N
D/I	0.9031	likely_pathogenic	0.911	pathogenic	0.194	Stabilizing	0.995	D	0.737	prob.delet.	None	None	None	None	N
D/K	0.8906	likely_pathogenic	0.8736	pathogenic	0.431	Stabilizing	0.982	D	0.703	prob.neutral	None	None	None	None	N
D/L	0.8604	likely_pathogenic	0.8691	pathogenic	0.194	Stabilizing	0.991	D	0.724	prob.delet.	None	None	None	None	N
D/M	0.9283	likely_pathogenic	0.9343	pathogenic	0.295	Stabilizing	1.0	D	0.661	neutral	None	None	None	None	N
D/N	0.279	likely_benign	0.2626	benign	0.093	Stabilizing	0.988	D	0.672	neutral	N	0.503184062	None	None	N
D/P	0.9844	likely_pathogenic	0.9871	pathogenic	0.074	Stabilizing	0.995	D	0.753	deleterious	None	None	None	None	N
D/Q	0.7815	likely_pathogenic	0.7537	pathogenic	0.126	Stabilizing	0.982	D	0.717	prob.delet.	None	None	None	None	N
D/R	0.8913	likely_pathogenic	0.8872	pathogenic	0.57	Stabilizing	0.991	D	0.691	prob.neutral	None	None	None	None	N
D/S	0.4593	ambiguous	0.4409	ambiguous	0.012	Stabilizing	0.968	D	0.65	neutral	None	None	None	None	N
D/T	0.7456	likely_pathogenic	0.749	pathogenic	0.157	Stabilizing	0.991	D	0.744	deleterious	None	None	None	None	N
D/V	0.7728	likely_pathogenic	0.7852	pathogenic	0.074	Stabilizing	0.994	D	0.737	prob.delet.	N	0.490575903	None	None	N
D/W	0.9871	likely_pathogenic	0.9874	pathogenic	-0.07	Destabilizing	1.0	D	0.673	neutral	None	None	None	None	N
D/Y	0.7114	likely_pathogenic	0.7246	pathogenic	0.047	Stabilizing	0.999	D	0.679	prob.neutral	N	0.505833002	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.