TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32468	97627;97628;97629	chr2:178542354;178542353;178542352	chr2:179407081;179407080;179407079
N2AB	30827	92704;92705;92706	chr2:178542354;178542353;178542352	chr2:179407081;179407080;179407079
N2A	29900	89923;89924;89925	chr2:178542354;178542353;178542352	chr2:179407081;179407080;179407079
N2B	23403	70432;70433;70434	chr2:178542354;178542353;178542352	chr2:179407081;179407080;179407079
Novex-1	23528	70807;70808;70809	chr2:178542354;178542353;178542352	chr2:179407081;179407080;179407079
Novex-2	23595	71008;71009;71010	chr2:178542354;178542353;178542352	chr2:179407081;179407080;179407079
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-124
• Domain position: 70
• Structural Position: 102
• Q(SASA): 0.3935
• 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
N/K	None	None	0.801	N	0.271	0.149	0.0551355673512	gnomAD-4.0.0	2.40134E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.62576E-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
N/A	0.1469	likely_benign	0.1058	benign	-0.848	Destabilizing	0.007	N	0.226	neutral	None	None	None	None	N
N/C	0.1477	likely_benign	0.116	benign	0.119	Stabilizing	0.998	D	0.431	neutral	None	None	None	None	N
N/D	0.171	likely_benign	0.1556	benign	-0.797	Destabilizing	0.801	D	0.294	neutral	N	0.451005803	None	None	N
N/E	0.3177	likely_benign	0.2858	benign	-0.714	Destabilizing	0.842	D	0.267	neutral	None	None	None	None	N
N/F	0.4341	ambiguous	0.3342	benign	-0.626	Destabilizing	0.974	D	0.448	neutral	None	None	None	None	N
N/G	0.2162	likely_benign	0.1598	benign	-1.185	Destabilizing	0.525	D	0.253	neutral	None	None	None	None	N
N/H	0.1028	likely_benign	0.0919	benign	-0.997	Destabilizing	0.989	D	0.361	neutral	N	0.419221458	None	None	N
N/I	0.1825	likely_benign	0.1413	benign	0.007	Stabilizing	0.934	D	0.457	neutral	N	0.437268502	None	None	N
N/K	0.2695	likely_benign	0.2374	benign	-0.366	Destabilizing	0.801	D	0.271	neutral	N	0.40642552	None	None	N
N/L	0.2052	likely_benign	0.149	benign	0.007	Stabilizing	0.728	D	0.331	neutral	None	None	None	None	N
N/M	0.2112	likely_benign	0.1631	benign	0.603	Stabilizing	0.998	D	0.395	neutral	None	None	None	None	N
N/P	0.9059	likely_pathogenic	0.8437	pathogenic	-0.249	Destabilizing	0.974	D	0.416	neutral	None	None	None	None	N
N/Q	0.2317	likely_benign	0.2049	benign	-0.957	Destabilizing	0.974	D	0.363	neutral	None	None	None	None	N
N/R	0.2789	likely_benign	0.2443	benign	-0.361	Destabilizing	0.842	D	0.353	neutral	None	None	None	None	N
N/S	0.0661	likely_benign	0.0575	benign	-0.903	Destabilizing	0.454	N	0.352	neutral	N	0.356978134	None	None	N
N/T	0.0869	likely_benign	0.0709	benign	-0.638	Destabilizing	0.007	N	0.065	neutral	N	0.321897194	None	None	N
N/V	0.1657	likely_benign	0.1264	benign	-0.249	Destabilizing	0.728	D	0.334	neutral	None	None	None	None	N
N/W	0.6884	likely_pathogenic	0.5958	pathogenic	-0.421	Destabilizing	0.998	D	0.505	neutral	None	None	None	None	N
N/Y	0.1584	likely_benign	0.1318	benign	-0.223	Destabilizing	0.989	D	0.409	neutral	N	0.499567754	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.