TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20622	62089;62090;62091	chr2:178589861;178589860;178589859	chr2:179454588;179454587;179454586
N2AB	18981	57166;57167;57168	chr2:178589861;178589860;178589859	chr2:179454588;179454587;179454586
N2A	18054	54385;54386;54387	chr2:178589861;178589860;178589859	chr2:179454588;179454587;179454586
N2B	11557	34894;34895;34896	chr2:178589861;178589860;178589859	chr2:179454588;179454587;179454586
Novex-1	11682	35269;35270;35271	chr2:178589861;178589860;178589859	chr2:179454588;179454587;179454586
Novex-2	11749	35470;35471;35472	chr2:178589861;178589860;178589859	chr2:179454588;179454587;179454586
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-37
• Domain position: 54
• Structural Position: 75
• Q(SASA): 0.6283
• Predicted PPI site: I

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/E	None	None	0.006	N	0.179	0.108	0.259761712551	gnomAD-4.0.0	1.59201E-06	None	None	None	None	I	None	0	0	None	4.76781E-05	0	None	0	0	0	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	0.3849	ambiguous	0.3944	ambiguous	-0.078	Destabilizing	0.324	N	0.384	neutral	N	0.442172889	None	None	I
D/C	0.8432	likely_pathogenic	0.8504	pathogenic	0.288	Stabilizing	0.981	D	0.473	neutral	None	None	None	None	I
D/E	0.2729	likely_benign	0.2989	benign	-0.23	Destabilizing	0.006	N	0.179	neutral	N	0.464972391	None	None	I
D/F	0.8518	likely_pathogenic	0.8465	pathogenic	-0.254	Destabilizing	0.818	D	0.413	neutral	None	None	None	None	I
D/G	0.323	likely_benign	0.3684	ambiguous	-0.219	Destabilizing	0.193	N	0.365	neutral	N	0.46223873	None	None	I
D/H	0.5366	ambiguous	0.5573	ambiguous	-0.021	Destabilizing	0.003	N	0.252	neutral	N	0.471823792	None	None	I
D/I	0.7659	likely_pathogenic	0.7268	pathogenic	0.228	Stabilizing	0.818	D	0.421	neutral	None	None	None	None	I
D/K	0.664	likely_pathogenic	0.6612	pathogenic	0.617	Stabilizing	0.241	N	0.343	neutral	None	None	None	None	I
D/L	0.7295	likely_pathogenic	0.6938	pathogenic	0.228	Stabilizing	0.69	D	0.391	neutral	None	None	None	None	I
D/M	0.8616	likely_pathogenic	0.84	pathogenic	0.346	Stabilizing	0.981	D	0.409	neutral	None	None	None	None	I
D/N	0.1407	likely_benign	0.1555	benign	0.429	Stabilizing	0.001	N	0.105	neutral	N	0.431841252	None	None	I
D/P	0.9039	likely_pathogenic	0.8875	pathogenic	0.147	Stabilizing	0.818	D	0.372	neutral	None	None	None	None	I
D/Q	0.6107	likely_pathogenic	0.6154	pathogenic	0.42	Stabilizing	0.69	D	0.351	neutral	None	None	None	None	I
D/R	0.707	likely_pathogenic	0.7132	pathogenic	0.664	Stabilizing	0.69	D	0.377	neutral	None	None	None	None	I
D/S	0.236	likely_benign	0.2495	benign	0.342	Stabilizing	0.241	N	0.346	neutral	None	None	None	None	I
D/T	0.4151	ambiguous	0.403	ambiguous	0.448	Stabilizing	0.241	N	0.385	neutral	None	None	None	None	I
D/V	0.5576	ambiguous	0.5178	ambiguous	0.147	Stabilizing	0.773	D	0.397	neutral	N	0.459163926	None	None	I
D/W	0.9716	likely_pathogenic	0.9666	pathogenic	-0.211	Destabilizing	0.981	D	0.567	neutral	None	None	None	None	I
D/Y	0.5204	ambiguous	0.4949	ambiguous	-0.025	Destabilizing	0.627	D	0.425	neutral	N	0.498759677	None	None	I

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.