TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19437	58534;58535;58536	chr2:178594084;178594083;178594082	chr2:179458811;179458810;179458809
N2AB	17796	53611;53612;53613	chr2:178594084;178594083;178594082	chr2:179458811;179458810;179458809
N2A	16869	50830;50831;50832	chr2:178594084;178594083;178594082	chr2:179458811;179458810;179458809
N2B	10372	31339;31340;31341	chr2:178594084;178594083;178594082	chr2:179458811;179458810;179458809
Novex-1	10497	31714;31715;31716	chr2:178594084;178594083;178594082	chr2:179458811;179458810;179458809
Novex-2	10564	31915;31916;31917	chr2:178594084;178594083;178594082	chr2:179458811;179458810;179458809
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-118
• Domain position: 47
• Structural Position: 127
• Q(SASA): 0.6554
• 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
T/A	rs778067188	-0.481	0.349	N	0.555	0.206	None	gnomAD-2.1.1	1.07E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	2.35E-05	0
T/A	rs778067188	-0.481	0.349	N	0.555	0.206	None	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	4.41E-05	0	0
T/A	rs778067188	-0.481	0.349	N	0.555	0.206	None	gnomAD-4.0.0	3.71902E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.00148E-05	0	1.60143E-05

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
T/A	0.0904	likely_benign	0.0925	benign	-0.643	Destabilizing	0.349	N	0.555	neutral	N	0.488439188	None	None	N
T/C	0.4036	ambiguous	0.362	ambiguous	-0.37	Destabilizing	0.996	D	0.681	prob.neutral	None	None	None	None	N
T/D	0.3111	likely_benign	0.361	ambiguous	0.345	Stabilizing	0.923	D	0.647	neutral	None	None	None	None	N
T/E	0.244	likely_benign	0.2677	benign	0.339	Stabilizing	0.923	D	0.649	neutral	None	None	None	None	N
T/F	0.239	likely_benign	0.2222	benign	-0.831	Destabilizing	0.923	D	0.755	deleterious	None	None	None	None	N
T/G	0.2867	likely_benign	0.2836	benign	-0.879	Destabilizing	0.633	D	0.697	prob.neutral	None	None	None	None	N
T/H	0.2592	likely_benign	0.2588	benign	-1.153	Destabilizing	0.996	D	0.761	deleterious	None	None	None	None	N
T/I	0.1443	likely_benign	0.1263	benign	-0.117	Destabilizing	0.018	N	0.415	neutral	N	0.516492581	None	None	N
T/K	0.2348	likely_benign	0.2495	benign	-0.41	Destabilizing	0.923	D	0.649	neutral	None	None	None	None	N
T/L	0.0989	likely_benign	0.0945	benign	-0.117	Destabilizing	0.372	N	0.607	neutral	None	None	None	None	N
T/M	0.0874	likely_benign	0.0808	benign	0.019	Stabilizing	0.979	D	0.676	prob.neutral	None	None	None	None	N
T/N	0.0976	likely_benign	0.1056	benign	-0.331	Destabilizing	0.901	D	0.63	neutral	N	0.446227206	None	None	N
T/P	0.1954	likely_benign	0.2213	benign	-0.26	Destabilizing	0.949	D	0.695	prob.neutral	N	0.521687757	None	None	N
T/Q	0.2324	likely_benign	0.2339	benign	-0.444	Destabilizing	0.961	D	0.681	prob.neutral	None	None	None	None	N
T/R	0.2123	likely_benign	0.2235	benign	-0.269	Destabilizing	0.923	D	0.69	prob.neutral	None	None	None	None	N
T/S	0.1152	likely_benign	0.1134	benign	-0.648	Destabilizing	0.034	N	0.318	neutral	N	0.471354937	None	None	N
T/V	0.1188	likely_benign	0.1034	benign	-0.26	Destabilizing	0.372	N	0.571	neutral	None	None	None	None	N
T/W	0.5895	likely_pathogenic	0.5784	pathogenic	-0.786	Destabilizing	0.996	D	0.759	deleterious	None	None	None	None	N
T/Y	0.2355	likely_benign	0.2358	benign	-0.52	Destabilizing	0.961	D	0.76	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.