TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20659	62200;62201;62202	chr2:178589750;178589749;178589748	chr2:179454477;179454476;179454475
N2AB	19018	57277;57278;57279	chr2:178589750;178589749;178589748	chr2:179454477;179454476;179454475
N2A	18091	54496;54497;54498	chr2:178589750;178589749;178589748	chr2:179454477;179454476;179454475
N2B	11594	35005;35006;35007	chr2:178589750;178589749;178589748	chr2:179454477;179454476;179454475
Novex-1	11719	35380;35381;35382	chr2:178589750;178589749;178589748	chr2:179454477;179454476;179454475
Novex-2	11786	35581;35582;35583	chr2:178589750;178589749;178589748	chr2:179454477;179454476;179454475
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Fn3-37
• Domain position: 91
• Structural Position: 126
• Q(SASA): 0.256
• 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
P/R	None	None	1.0	N	0.867	0.486	0.603037435086	gnomAD-4.0.0	1.59179E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85951E-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
P/A	0.1597	likely_benign	0.1435	benign	-1.331	Destabilizing	0.999	D	0.863	deleterious	N	0.47905283	None	None	N
P/C	0.8808	likely_pathogenic	0.8411	pathogenic	-0.776	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
P/D	0.9824	likely_pathogenic	0.9755	pathogenic	-0.983	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
P/E	0.9297	likely_pathogenic	0.8893	pathogenic	-0.967	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
P/F	0.9849	likely_pathogenic	0.9772	pathogenic	-0.938	Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	N
P/G	0.7293	likely_pathogenic	0.7389	pathogenic	-1.66	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
P/H	0.8841	likely_pathogenic	0.8555	pathogenic	-1.117	Destabilizing	1.0	D	0.825	deleterious	N	0.521301728	None	None	N
P/I	0.9499	likely_pathogenic	0.9181	pathogenic	-0.528	Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
P/K	0.943	likely_pathogenic	0.9149	pathogenic	-1.081	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
P/L	0.8141	likely_pathogenic	0.7484	pathogenic	-0.528	Destabilizing	1.0	D	0.886	deleterious	N	0.500662577	None	None	N
P/M	0.9268	likely_pathogenic	0.8995	pathogenic	-0.396	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
P/N	0.9367	likely_pathogenic	0.9299	pathogenic	-0.881	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
P/Q	0.81	likely_pathogenic	0.7559	pathogenic	-1.011	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
P/R	0.8737	likely_pathogenic	0.8225	pathogenic	-0.587	Destabilizing	1.0	D	0.867	deleterious	N	0.520541259	None	None	N
P/S	0.5249	ambiguous	0.4817	ambiguous	-1.425	Destabilizing	1.0	D	0.891	deleterious	N	0.480787577	None	None	N
P/T	0.6913	likely_pathogenic	0.5965	pathogenic	-1.295	Destabilizing	1.0	D	0.885	deleterious	N	0.50851339	None	None	N
P/V	0.8427	likely_pathogenic	0.7725	pathogenic	-0.761	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
P/W	0.9918	likely_pathogenic	0.9878	pathogenic	-1.145	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
P/Y	0.9788	likely_pathogenic	0.9709	pathogenic	-0.839	Destabilizing	1.0	D	0.868	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.