TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33719	101380;101381;101382	chr2:178535460;178535459;178535458	chr2:179400187;179400186;179400185
N2AB	32078	96457;96458;96459	chr2:178535460;178535459;178535458	chr2:179400187;179400186;179400185
N2A	31151	93676;93677;93678	chr2:178535460;178535459;178535458	chr2:179400187;179400186;179400185
N2B	24654	74185;74186;74187	chr2:178535460;178535459;178535458	chr2:179400187;179400186;179400185
Novex-1	24779	74560;74561;74562	chr2:178535460;178535459;178535458	chr2:179400187;179400186;179400185
Novex-2	24846	74761;74762;74763	chr2:178535460;178535459;178535458	chr2:179400187;179400186;179400185
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Fn3-132
• Domain position: 31
• Structural Position: 33
• Q(SASA): 0.1621
• 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
S/C	rs2154136682	None	1.0	N	0.739	0.547	0.40032279838	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
S/A	0.2288	likely_benign	0.179	benign	-0.838	Destabilizing	0.92	D	0.607	neutral	None	None	None	None	N
S/C	0.1908	likely_benign	0.1507	benign	-0.51	Destabilizing	1.0	D	0.739	prob.delet.	N	0.478298226	None	None	N
S/D	0.9059	likely_pathogenic	0.8576	pathogenic	-0.107	Destabilizing	0.999	D	0.702	prob.neutral	None	None	None	None	N
S/E	0.9032	likely_pathogenic	0.8638	pathogenic	-0.116	Destabilizing	0.999	D	0.69	prob.neutral	None	None	None	None	N
S/F	0.7138	likely_pathogenic	0.5834	pathogenic	-1.105	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
S/G	0.3573	ambiguous	0.2495	benign	-1.069	Destabilizing	0.999	D	0.617	neutral	N	0.479047651	None	None	N
S/H	0.7983	likely_pathogenic	0.7307	pathogenic	-1.542	Destabilizing	1.0	D	0.74	deleterious	None	None	None	None	N
S/I	0.7761	likely_pathogenic	0.6323	pathogenic	-0.328	Destabilizing	1.0	D	0.763	deleterious	N	0.508301764	None	None	N
S/K	0.9797	likely_pathogenic	0.9638	pathogenic	-0.631	Destabilizing	1.0	D	0.696	prob.neutral	None	None	None	None	N
S/L	0.4665	ambiguous	0.3315	benign	-0.328	Destabilizing	0.999	D	0.702	prob.neutral	None	None	None	None	N
S/M	0.6112	likely_pathogenic	0.4804	ambiguous	0.044	Stabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
S/N	0.6023	likely_pathogenic	0.4725	ambiguous	-0.566	Destabilizing	0.985	D	0.701	prob.neutral	N	0.492172519	None	None	N
S/P	0.9928	likely_pathogenic	0.9846	pathogenic	-0.465	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
S/Q	0.8761	likely_pathogenic	0.8196	pathogenic	-0.739	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
S/R	0.9606	likely_pathogenic	0.9295	pathogenic	-0.534	Destabilizing	1.0	D	0.747	deleterious	N	0.491132108	None	None	N
S/T	0.2941	likely_benign	0.2274	benign	-0.635	Destabilizing	0.308	N	0.505	neutral	N	0.478093962	None	None	N
S/V	0.6758	likely_pathogenic	0.5184	ambiguous	-0.465	Destabilizing	0.999	D	0.741	deleterious	None	None	None	None	N
S/W	0.7898	likely_pathogenic	0.7182	pathogenic	-1.041	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
S/Y	0.6301	likely_pathogenic	0.5157	ambiguous	-0.787	Destabilizing	1.0	D	0.759	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.