TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6368	19327;19328;19329	chr2:178728936;178728935;178728934	chr2:179593663;179593662;179593661
N2AB	6051	18376;18377;18378	chr2:178728936;178728935;178728934	chr2:179593663;179593662;179593661
N2A	5124	15595;15596;15597	chr2:178728936;178728935;178728934	chr2:179593663;179593662;179593661
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-47
• Domain position: 77
• Structural Position: 161
• Q(SASA): 0.1554
• 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/S	rs748146062	-0.828	0.999	N	0.587	0.536	0.350964488264	gnomAD-2.1.1	1.22E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	2.69E-05	0
N/S	rs748146062	-0.828	0.999	N	0.587	0.536	0.350964488264	gnomAD-4.0.0	4.79001E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.60003E-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	0.9905	likely_pathogenic	0.9879	pathogenic	-0.77	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
N/C	0.9831	likely_pathogenic	0.9781	pathogenic	-0.192	Destabilizing	1.0	D	0.686	prob.neutral	None	None	None	None	N
N/D	0.9399	likely_pathogenic	0.9349	pathogenic	-1.299	Destabilizing	0.999	D	0.624	neutral	D	0.55999441	None	None	N
N/E	0.993	likely_pathogenic	0.993	pathogenic	-1.23	Destabilizing	0.999	D	0.715	prob.delet.	None	None	None	None	N
N/F	0.9986	likely_pathogenic	0.9985	pathogenic	-0.795	Destabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	N
N/G	0.9668	likely_pathogenic	0.9661	pathogenic	-1.051	Destabilizing	0.999	D	0.563	neutral	None	None	None	None	N
N/H	0.9656	likely_pathogenic	0.9628	pathogenic	-0.912	Destabilizing	1.0	D	0.732	prob.delet.	D	0.549905552	None	None	N
N/I	0.9865	likely_pathogenic	0.9817	pathogenic	-0.074	Destabilizing	1.0	D	0.711	prob.delet.	D	0.561515347	None	None	N
N/K	0.994	likely_pathogenic	0.994	pathogenic	-0.211	Destabilizing	1.0	D	0.729	prob.delet.	D	0.560754878	None	None	N
N/L	0.9807	likely_pathogenic	0.9763	pathogenic	-0.074	Destabilizing	1.0	D	0.722	prob.delet.	None	None	None	None	N
N/M	0.9834	likely_pathogenic	0.9785	pathogenic	0.474	Stabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
N/P	0.997	likely_pathogenic	0.9975	pathogenic	-0.278	Destabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	N
N/Q	0.9949	likely_pathogenic	0.9947	pathogenic	-1.072	Destabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	N
N/R	0.9938	likely_pathogenic	0.9943	pathogenic	-0.09	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
N/S	0.8112	likely_pathogenic	0.7918	pathogenic	-0.816	Destabilizing	0.999	D	0.587	neutral	N	0.495286391	None	None	N
N/T	0.93	likely_pathogenic	0.9148	pathogenic	-0.584	Destabilizing	0.999	D	0.705	prob.neutral	D	0.533749853	None	None	N
N/V	0.9861	likely_pathogenic	0.9818	pathogenic	-0.278	Destabilizing	1.0	D	0.72	prob.delet.	None	None	None	None	N
N/W	0.9993	likely_pathogenic	0.9992	pathogenic	-0.596	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	N
N/Y	0.9805	likely_pathogenic	0.9783	pathogenic	-0.316	Destabilizing	1.0	D	0.731	prob.delet.	D	0.561261857	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.