TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33042	99349;99350;99351	chr2:178538705;178538704;178538703	chr2:179403432;179403431;179403430
N2AB	31401	94426;94427;94428	chr2:178538705;178538704;178538703	chr2:179403432;179403431;179403430
N2A	30474	91645;91646;91647	chr2:178538705;178538704;178538703	chr2:179403432;179403431;179403430
N2B	23977	72154;72155;72156	chr2:178538705;178538704;178538703	chr2:179403432;179403431;179403430
Novex-1	24102	72529;72530;72531	chr2:178538705;178538704;178538703	chr2:179403432;179403431;179403430
Novex-2	24169	72730;72731;72732	chr2:178538705;178538704;178538703	chr2:179403432;179403431;179403430
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Fn3-129
• Domain position: 45
• Structural Position: 62
• Q(SASA): 0.2632
• 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/N	None	None	0.982	N	0.482	0.254	0.307966526162	gnomAD-4.0.0	4.77398E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.57545E-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
D/A	0.2021	likely_benign	0.2399	benign	-0.421	Destabilizing	0.939	D	0.415	neutral	N	0.460662649	None	None	N
D/C	0.6178	likely_pathogenic	0.6846	pathogenic	0.054	Stabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	N
D/E	0.0973	likely_benign	0.1061	benign	-0.445	Destabilizing	0.02	N	0.247	neutral	N	0.425163209	None	None	N
D/F	0.5766	likely_pathogenic	0.6668	pathogenic	-0.382	Destabilizing	0.999	D	0.679	prob.neutral	None	None	None	None	N
D/G	0.2139	likely_benign	0.258	benign	-0.644	Destabilizing	0.939	D	0.411	neutral	N	0.439977946	None	None	N
D/H	0.4182	ambiguous	0.4683	ambiguous	-0.442	Destabilizing	0.998	D	0.559	neutral	N	0.468282055	None	None	N
D/I	0.3536	ambiguous	0.4315	ambiguous	0.128	Stabilizing	0.993	D	0.658	neutral	None	None	None	None	N
D/K	0.4432	ambiguous	0.4913	ambiguous	0.167	Stabilizing	0.91	D	0.409	neutral	None	None	None	None	N
D/L	0.3919	ambiguous	0.4591	ambiguous	0.128	Stabilizing	0.986	D	0.617	neutral	None	None	None	None	N
D/M	0.5528	ambiguous	0.63	pathogenic	0.438	Stabilizing	0.999	D	0.693	prob.neutral	None	None	None	None	N
D/N	0.1236	likely_benign	0.1466	benign	-0.107	Destabilizing	0.982	D	0.482	neutral	N	0.465817753	None	None	N
D/P	0.8389	likely_pathogenic	0.8729	pathogenic	-0.033	Destabilizing	0.993	D	0.5	neutral	None	None	None	None	N
D/Q	0.3441	ambiguous	0.3824	ambiguous	-0.079	Destabilizing	0.973	D	0.488	neutral	None	None	None	None	N
D/R	0.5553	ambiguous	0.5975	pathogenic	0.266	Stabilizing	0.986	D	0.529	neutral	None	None	None	None	N
D/S	0.1475	likely_benign	0.1698	benign	-0.241	Destabilizing	0.953	D	0.373	neutral	None	None	None	None	N
D/T	0.2582	likely_benign	0.2966	benign	-0.067	Destabilizing	0.986	D	0.487	neutral	None	None	None	None	N
D/V	0.2322	likely_benign	0.2836	benign	-0.033	Destabilizing	0.991	D	0.623	neutral	N	0.464492388	None	None	N
D/W	0.8974	likely_pathogenic	0.9224	pathogenic	-0.241	Destabilizing	0.999	D	0.72	prob.delet.	None	None	None	None	N
D/Y	0.2992	likely_benign	0.3655	ambiguous	-0.143	Destabilizing	0.999	D	0.679	prob.neutral	N	0.503818781	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.