TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29028	87307;87308;87309	chr2:178558377;178558376;178558375	chr2:179423104;179423103;179423102
N2AB	27387	82384;82385;82386	chr2:178558377;178558376;178558375	chr2:179423104;179423103;179423102
N2A	26460	79603;79604;79605	chr2:178558377;178558376;178558375	chr2:179423104;179423103;179423102
N2B	19963	60112;60113;60114	chr2:178558377;178558376;178558375	chr2:179423104;179423103;179423102
Novex-1	20088	60487;60488;60489	chr2:178558377;178558376;178558375	chr2:179423104;179423103;179423102
Novex-2	20155	60688;60689;60690	chr2:178558377;178558376;178558375	chr2:179423104;179423103;179423102
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-99
• Domain position: 87
• Structural Position: 122
• Q(SASA): 0.3709
• 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	None	None	0.991	N	0.746	0.359	0.355034743287	gnomAD-4.0.0	1.59191E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85855E-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	0.3235	likely_benign	0.3151	benign	-0.061	Destabilizing	0.991	D	0.746	deleterious	N	0.498084887	None	None	N
E/C	0.9286	likely_pathogenic	0.9199	pathogenic	-0.079	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
E/D	0.2514	likely_benign	0.2509	benign	-1.015	Destabilizing	0.149	N	0.305	neutral	N	0.466164469	None	None	N
E/F	0.8696	likely_pathogenic	0.8655	pathogenic	0.854	Stabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
E/G	0.4533	ambiguous	0.4435	ambiguous	-0.496	Destabilizing	0.995	D	0.77	deleterious	N	0.518998877	None	None	N
E/H	0.7616	likely_pathogenic	0.7418	pathogenic	0.677	Stabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
E/I	0.4764	ambiguous	0.4617	ambiguous	1.141	Stabilizing	0.999	D	0.799	deleterious	None	None	None	None	N
E/K	0.492	ambiguous	0.4326	ambiguous	-0.237	Destabilizing	0.982	D	0.743	deleterious	N	0.510918111	None	None	N
E/L	0.5349	ambiguous	0.5295	ambiguous	1.141	Stabilizing	0.998	D	0.726	deleterious	None	None	None	None	N
E/M	0.5685	likely_pathogenic	0.557	ambiguous	1.415	Stabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
E/N	0.5165	ambiguous	0.4913	ambiguous	-0.962	Destabilizing	0.996	D	0.811	deleterious	None	None	None	None	N
E/P	0.6538	likely_pathogenic	0.6566	pathogenic	0.763	Stabilizing	0.999	D	0.772	deleterious	None	None	None	None	N
E/Q	0.2579	likely_benign	0.2395	benign	-0.711	Destabilizing	0.998	D	0.799	deleterious	N	0.502933346	None	None	N
E/R	0.6717	likely_pathogenic	0.6282	pathogenic	0.054	Stabilizing	0.998	D	0.797	deleterious	None	None	None	None	N
E/S	0.4172	ambiguous	0.4039	ambiguous	-1.293	Destabilizing	0.987	D	0.746	deleterious	None	None	None	None	N
E/T	0.4132	ambiguous	0.386	ambiguous	-0.907	Destabilizing	0.998	D	0.74	deleterious	None	None	None	None	N
E/V	0.2898	likely_benign	0.2802	benign	0.763	Stabilizing	0.999	D	0.751	deleterious	N	0.516268003	None	None	N
E/W	0.9711	likely_pathogenic	0.9699	pathogenic	1.027	Stabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
E/Y	0.7967	likely_pathogenic	0.7898	pathogenic	1.128	Stabilizing	1.0	D	0.843	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.