TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28973	87142;87143;87144	chr2:178558542;178558541;178558540	chr2:179423269;179423268;179423267
N2AB	27332	82219;82220;82221	chr2:178558542;178558541;178558540	chr2:179423269;179423268;179423267
N2A	26405	79438;79439;79440	chr2:178558542;178558541;178558540	chr2:179423269;179423268;179423267
N2B	19908	59947;59948;59949	chr2:178558542;178558541;178558540	chr2:179423269;179423268;179423267
Novex-1	20033	60322;60323;60324	chr2:178558542;178558541;178558540	chr2:179423269;179423268;179423267
Novex-2	20100	60523;60524;60525	chr2:178558542;178558541;178558540	chr2:179423269;179423268;179423267
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Fn3-99
• Domain position: 32
• Structural Position: 34
• Q(SASA): 0.6613
• 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
R/K	None	None	0.003	N	0.309	0.128	0.21279746466	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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
R/A	0.5775	likely_pathogenic	0.7087	pathogenic	0.044	Stabilizing	0.912	D	0.619	neutral	None	None	None	None	I
R/C	0.2804	likely_benign	0.3784	ambiguous	-0.181	Destabilizing	0.999	D	0.695	prob.neutral	None	None	None	None	I
R/D	0.8502	likely_pathogenic	0.9094	pathogenic	-0.157	Destabilizing	0.973	D	0.627	neutral	None	None	None	None	I
R/E	0.6241	likely_pathogenic	0.7415	pathogenic	-0.096	Destabilizing	0.608	D	0.569	neutral	None	None	None	None	I
R/F	0.7531	likely_pathogenic	0.8378	pathogenic	-0.197	Destabilizing	0.989	D	0.66	neutral	None	None	None	None	I
R/G	0.4786	ambiguous	0.6135	pathogenic	-0.139	Destabilizing	0.886	D	0.555	neutral	N	0.495642014	None	None	I
R/H	0.163	likely_benign	0.2189	benign	-0.645	Destabilizing	0.989	D	0.583	neutral	None	None	None	None	I
R/I	0.4808	ambiguous	0.6035	pathogenic	0.485	Stabilizing	0.958	D	0.671	neutral	N	0.517902799	None	None	I
R/K	0.117	likely_benign	0.1353	benign	-0.087	Destabilizing	0.003	N	0.309	neutral	N	0.430686459	None	None	I
R/L	0.4319	ambiguous	0.5606	ambiguous	0.485	Stabilizing	0.81	D	0.555	neutral	None	None	None	None	I
R/M	0.4936	ambiguous	0.6151	pathogenic	0.011	Stabilizing	0.997	D	0.575	neutral	None	None	None	None	I
R/N	0.7938	likely_pathogenic	0.8641	pathogenic	0.062	Stabilizing	0.973	D	0.551	neutral	None	None	None	None	I
R/P	0.4957	ambiguous	0.6427	pathogenic	0.358	Stabilizing	0.987	D	0.643	neutral	None	None	None	None	I
R/Q	0.1806	likely_benign	0.2361	benign	0.001	Stabilizing	0.964	D	0.561	neutral	None	None	None	None	I
R/S	0.7447	likely_pathogenic	0.8347	pathogenic	-0.212	Destabilizing	0.886	D	0.593	neutral	N	0.479691127	None	None	I
R/T	0.5362	ambiguous	0.6754	pathogenic	-0.023	Destabilizing	0.965	D	0.554	neutral	N	0.476093462	None	None	I
R/V	0.5231	ambiguous	0.642	pathogenic	0.358	Stabilizing	0.957	D	0.669	neutral	None	None	None	None	I
R/W	0.2951	likely_benign	0.3942	ambiguous	-0.302	Destabilizing	0.999	D	0.717	prob.delet.	None	None	None	None	I
R/Y	0.5692	likely_pathogenic	0.6795	pathogenic	0.111	Stabilizing	0.989	D	0.644	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.