TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23563	70912;70913;70914	chr2:178575445;178575444;178575443	chr2:179440172;179440171;179440170
N2AB	21922	65989;65990;65991	chr2:178575445;178575444;178575443	chr2:179440172;179440171;179440170
N2A	20995	63208;63209;63210	chr2:178575445;178575444;178575443	chr2:179440172;179440171;179440170
N2B	14498	43717;43718;43719	chr2:178575445;178575444;178575443	chr2:179440172;179440171;179440170
Novex-1	14623	44092;44093;44094	chr2:178575445;178575444;178575443	chr2:179440172;179440171;179440170
Novex-2	14690	44293;44294;44295	chr2:178575445;178575444;178575443	chr2:179440172;179440171;179440170
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-59
• Domain position: 32
• Structural Position: 34
• Q(SASA): 0.7095
• 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
K/N	rs775933082	None	0.549	N	0.371	0.181	0.193865811164	gnomAD-4.0.0	6.84314E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99594E-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
K/A	0.6387	likely_pathogenic	0.6394	pathogenic	0.019	Stabilizing	0.4	N	0.435	neutral	None	None	None	None	I
K/C	0.8412	likely_pathogenic	0.8631	pathogenic	-0.191	Destabilizing	0.992	D	0.457	neutral	None	None	None	None	I
K/D	0.9037	likely_pathogenic	0.9019	pathogenic	0.066	Stabilizing	0.766	D	0.441	neutral	None	None	None	None	I
K/E	0.6146	likely_pathogenic	0.6103	pathogenic	0.054	Stabilizing	0.549	D	0.351	neutral	N	0.462297445	None	None	I
K/F	0.9201	likely_pathogenic	0.9301	pathogenic	-0.305	Destabilizing	0.85	D	0.485	neutral	None	None	None	None	I
K/G	0.7833	likely_pathogenic	0.7934	pathogenic	-0.142	Destabilizing	0.617	D	0.479	neutral	None	None	None	None	I
K/H	0.5029	ambiguous	0.522	ambiguous	-0.403	Destabilizing	0.92	D	0.41	neutral	None	None	None	None	I
K/I	0.5916	likely_pathogenic	0.6114	pathogenic	0.354	Stabilizing	0.447	N	0.477	neutral	None	None	None	None	I
K/L	0.601	likely_pathogenic	0.626	pathogenic	0.354	Stabilizing	0.002	N	0.168	neutral	None	None	None	None	I
K/M	0.533	ambiguous	0.5375	ambiguous	0.218	Stabilizing	0.81	D	0.419	neutral	N	0.474130716	None	None	I
K/N	0.8288	likely_pathogenic	0.8269	pathogenic	0.307	Stabilizing	0.549	D	0.371	neutral	N	0.515806643	None	None	I
K/P	0.6505	likely_pathogenic	0.6639	pathogenic	0.268	Stabilizing	0.005	N	0.299	neutral	None	None	None	None	I
K/Q	0.3107	likely_benign	0.3188	benign	0.102	Stabilizing	0.549	D	0.39	neutral	N	0.470545864	None	None	I
K/R	0.067	likely_benign	0.0707	benign	0.073	Stabilizing	0.002	N	0.137	neutral	N	0.452584671	None	None	I
K/S	0.8003	likely_pathogenic	0.8088	pathogenic	-0.174	Destabilizing	0.617	D	0.348	neutral	None	None	None	None	I
K/T	0.5267	ambiguous	0.5291	ambiguous	-0.05	Destabilizing	0.549	D	0.451	neutral	D	0.523636692	None	None	I
K/V	0.5275	ambiguous	0.5467	ambiguous	0.268	Stabilizing	0.447	N	0.493	neutral	None	None	None	None	I
K/W	0.8701	likely_pathogenic	0.8878	pathogenic	-0.331	Destabilizing	0.992	D	0.504	neutral	None	None	None	None	I
K/Y	0.8363	likely_pathogenic	0.8419	pathogenic	0.04	Stabilizing	0.972	D	0.469	neutral	None	None	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.