TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29794	89605;89606;89607	chr2:178553625;178553624;178553623	chr2:179418352;179418351;179418350
N2AB	28153	84682;84683;84684	chr2:178553625;178553624;178553623	chr2:179418352;179418351;179418350
N2A	27226	81901;81902;81903	chr2:178553625;178553624;178553623	chr2:179418352;179418351;179418350
N2B	20729	62410;62411;62412	chr2:178553625;178553624;178553623	chr2:179418352;179418351;179418350
Novex-1	20854	62785;62786;62787	chr2:178553625;178553624;178553623	chr2:179418352;179418351;179418350
Novex-2	20921	62986;62987;62988	chr2:178553625;178553624;178553623	chr2:179418352;179418351;179418350
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: Fn3-105
• Domain position: 61
• Structural Position: 90
• Q(SASA): 0.6299
• 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/D	rs1700216447	None	0.999	N	0.507	0.229	0.188950314367	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31252E-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	0.3346	likely_benign	0.2856	benign	-0.889	Destabilizing	0.999	D	0.676	prob.neutral	N	0.502087984	None	None	N
E/C	0.9297	likely_pathogenic	0.9248	pathogenic	-0.455	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
E/D	0.3485	ambiguous	0.3132	benign	-0.948	Destabilizing	0.999	D	0.507	neutral	N	0.492715497	None	None	N
E/F	0.9451	likely_pathogenic	0.9317	pathogenic	-0.155	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
E/G	0.4511	ambiguous	0.3829	ambiguous	-1.261	Destabilizing	1.0	D	0.693	prob.neutral	N	0.472458421	None	None	N
E/H	0.6961	likely_pathogenic	0.6794	pathogenic	-0.267	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
E/I	0.7052	likely_pathogenic	0.648	pathogenic	0.131	Stabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
E/K	0.3296	likely_benign	0.2833	benign	-0.446	Destabilizing	0.999	D	0.605	neutral	N	0.499471753	None	None	N
E/L	0.7945	likely_pathogenic	0.7513	pathogenic	0.131	Stabilizing	1.0	D	0.766	deleterious	None	None	None	None	N
E/M	0.7401	likely_pathogenic	0.692	pathogenic	0.511	Stabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
E/N	0.5025	ambiguous	0.4512	ambiguous	-1.036	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
E/P	0.9905	likely_pathogenic	0.9867	pathogenic	-0.188	Destabilizing	1.0	D	0.76	deleterious	None	None	None	None	N
E/Q	0.2039	likely_benign	0.189	benign	-0.888	Destabilizing	1.0	D	0.663	neutral	N	0.474613381	None	None	N
E/R	0.4771	ambiguous	0.4511	ambiguous	-0.08	Destabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	N
E/S	0.3361	likely_benign	0.3123	benign	-1.343	Destabilizing	0.999	D	0.677	prob.neutral	None	None	None	None	N
E/T	0.3809	ambiguous	0.3392	benign	-1.025	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
E/V	0.4882	ambiguous	0.4287	ambiguous	-0.188	Destabilizing	1.0	D	0.733	prob.delet.	N	0.516422718	None	None	N
E/W	0.9777	likely_pathogenic	0.9733	pathogenic	0.186	Stabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
E/Y	0.8673	likely_pathogenic	0.8476	pathogenic	0.132	Stabilizing	1.0	D	0.78	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.