TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31350	94273;94274;94275	chr2:178547578;178547577;178547576	chr2:179412305;179412304;179412303
N2AB	29709	89350;89351;89352	chr2:178547578;178547577;178547576	chr2:179412305;179412304;179412303
N2A	28782	86569;86570;86571	chr2:178547578;178547577;178547576	chr2:179412305;179412304;179412303
N2B	22285	67078;67079;67080	chr2:178547578;178547577;178547576	chr2:179412305;179412304;179412303
Novex-1	22410	67453;67454;67455	chr2:178547578;178547577;178547576	chr2:179412305;179412304;179412303
Novex-2	22477	67654;67655;67656	chr2:178547578;178547577;178547576	chr2:179412305;179412304;179412303
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-116
• Domain position: 43
• Structural Position: 44
• Q(SASA): 0.4069
• 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
E/Q	None	None	1.0	N	0.616	0.333	0.4018988957	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
E/A	0.3845	ambiguous	0.3656	ambiguous	-0.895	Destabilizing	0.999	D	0.665	neutral	D	0.526004994	None	None	N
E/C	0.9509	likely_pathogenic	0.9409	pathogenic	-0.49	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
E/D	0.3464	ambiguous	0.3397	benign	-1.201	Destabilizing	0.999	D	0.443	neutral	N	0.418357454	None	None	N
E/F	0.9594	likely_pathogenic	0.9579	pathogenic	-0.303	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
E/G	0.5506	ambiguous	0.5169	ambiguous	-1.276	Destabilizing	1.0	D	0.695	prob.neutral	N	0.475398164	None	None	N
E/H	0.8801	likely_pathogenic	0.8593	pathogenic	-0.628	Destabilizing	1.0	D	0.641	neutral	None	None	None	None	N
E/I	0.7202	likely_pathogenic	0.7165	pathogenic	0.151	Stabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
E/K	0.5697	likely_pathogenic	0.5584	ambiguous	-0.672	Destabilizing	0.999	D	0.584	neutral	N	0.501895983	None	None	N
E/L	0.7199	likely_pathogenic	0.7199	pathogenic	0.151	Stabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
E/M	0.7759	likely_pathogenic	0.7697	pathogenic	0.636	Stabilizing	1.0	D	0.692	prob.neutral	None	None	None	None	N
E/N	0.6745	likely_pathogenic	0.6736	pathogenic	-1.164	Destabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	N
E/P	0.7679	likely_pathogenic	0.7827	pathogenic	-0.176	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
E/Q	0.3574	ambiguous	0.3315	benign	-1.016	Destabilizing	1.0	D	0.616	neutral	N	0.516980079	None	None	N
E/R	0.7349	likely_pathogenic	0.7119	pathogenic	-0.405	Destabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	N
E/S	0.5757	likely_pathogenic	0.5584	ambiguous	-1.491	Destabilizing	0.999	D	0.622	neutral	None	None	None	None	N
E/T	0.6589	likely_pathogenic	0.6408	pathogenic	-1.171	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
E/V	0.5104	ambiguous	0.5021	ambiguous	-0.176	Destabilizing	1.0	D	0.768	deleterious	N	0.472435649	None	None	N
E/W	0.9892	likely_pathogenic	0.9875	pathogenic	-0.042	Destabilizing	1.0	D	0.744	deleterious	None	None	None	None	N
E/Y	0.9407	likely_pathogenic	0.9341	pathogenic	-0.046	Destabilizing	1.0	D	0.74	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.