TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20673	62242;62243;62244	chr2:178589708;178589707;178589706	chr2:179454435;179454434;179454433
N2AB	19032	57319;57320;57321	chr2:178589708;178589707;178589706	chr2:179454435;179454434;179454433
N2A	18105	54538;54539;54540	chr2:178589708;178589707;178589706	chr2:179454435;179454434;179454433
N2B	11608	35047;35048;35049	chr2:178589708;178589707;178589706	chr2:179454435;179454434;179454433
Novex-1	11733	35422;35423;35424	chr2:178589708;178589707;178589706	chr2:179454435;179454434;179454433
Novex-2	11800	35623;35624;35625	chr2:178589708;178589707;178589706	chr2:179454435;179454434;179454433
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: Fn3-38
• Domain position: 6
• Structural Position: 6
• Q(SASA): 0.2882
• 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/A	rs2049807287	None	0.999	N	0.751	0.307	0.475034548194	gnomAD-4.0.0	1.59178E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85943E-06	0	0
E/K	rs2049807795	None	0.999	N	0.654	0.344	0.46289702323	gnomAD-4.0.0	1.36862E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	1.73732E-04	8.99586E-07	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	0.6691	likely_pathogenic	0.5816	pathogenic	-0.697	Destabilizing	0.999	D	0.751	deleterious	N	0.462628306	None	None	N
E/C	0.9853	likely_pathogenic	0.9737	pathogenic	-0.471	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
E/D	0.8142	likely_pathogenic	0.694	pathogenic	-1.188	Destabilizing	0.999	D	0.525	neutral	N	0.495202084	None	None	N
E/F	0.988	likely_pathogenic	0.9779	pathogenic	-0.345	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
E/G	0.6957	likely_pathogenic	0.6291	pathogenic	-1.042	Destabilizing	1.0	D	0.797	deleterious	N	0.431054605	None	None	N
E/H	0.9577	likely_pathogenic	0.9327	pathogenic	-0.764	Destabilizing	1.0	D	0.72	prob.delet.	None	None	None	None	N
E/I	0.8571	likely_pathogenic	0.8059	pathogenic	0.234	Stabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
E/K	0.6793	likely_pathogenic	0.6055	pathogenic	-0.85	Destabilizing	0.999	D	0.654	neutral	N	0.503858853	None	None	N
E/L	0.9098	likely_pathogenic	0.8624	pathogenic	0.234	Stabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
E/M	0.9058	likely_pathogenic	0.866	pathogenic	0.616	Stabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
E/N	0.9148	likely_pathogenic	0.8534	pathogenic	-1.12	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
E/P	0.9943	likely_pathogenic	0.9867	pathogenic	-0.054	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
E/Q	0.439	ambiguous	0.4039	ambiguous	-0.987	Destabilizing	1.0	D	0.685	prob.neutral	N	0.47936584	None	None	N
E/R	0.7416	likely_pathogenic	0.7068	pathogenic	-0.629	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
E/S	0.7782	likely_pathogenic	0.6892	pathogenic	-1.413	Destabilizing	0.999	D	0.719	prob.delet.	None	None	None	None	N
E/T	0.7923	likely_pathogenic	0.712	pathogenic	-1.144	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
E/V	0.7134	likely_pathogenic	0.6307	pathogenic	-0.054	Destabilizing	1.0	D	0.844	deleterious	N	0.505072361	None	None	N
E/W	0.9951	likely_pathogenic	0.9906	pathogenic	-0.23	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
E/Y	0.9796	likely_pathogenic	0.965	pathogenic	-0.158	Destabilizing	1.0	D	0.848	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.