TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2761	8506;8507;8508	chr2:178770511;178770510;178770509	chr2:179635238;179635237;179635236
N2AB	2761	8506;8507;8508	chr2:178770511;178770510;178770509	chr2:179635238;179635237;179635236
N2A	2761	8506;8507;8508	chr2:178770511;178770510;178770509	chr2:179635238;179635237;179635236
N2B	2715	8368;8369;8370	chr2:178770511;178770510;178770509	chr2:179635238;179635237;179635236
Novex-1	2715	8368;8369;8370	chr2:178770511;178770510;178770509	chr2:179635238;179635237;179635236
Novex-2	2715	8368;8369;8370	chr2:178770511;178770510;178770509	chr2:179635238;179635237;179635236
Novex-3	2761	8506;8507;8508	chr2:178770511;178770510;178770509	chr2:179635238;179635237;179635236

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-17
• Domain position: 55
• Structural Position: 135
• Q(SASA): 0.1368
• 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
I/V	None	None	None	N	0.1	0.23	0.159798565429	gnomAD-4.0.0	4.10441E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.39577E-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
I/A	0.1091	likely_benign	0.1304	benign	-1.618	Destabilizing	0.007	N	0.285	neutral	None	None	None	None	N
I/C	0.3529	ambiguous	0.4465	ambiguous	-1.071	Destabilizing	0.356	N	0.532	neutral	None	None	None	None	N
I/D	0.2353	likely_benign	0.3194	benign	-0.713	Destabilizing	0.072	N	0.596	neutral	None	None	None	None	N
I/E	0.2078	likely_benign	0.2553	benign	-0.673	Destabilizing	0.072	N	0.585	neutral	None	None	None	None	N
I/F	0.1258	likely_benign	0.1479	benign	-1.033	Destabilizing	0.029	N	0.419	neutral	N	0.497328618	None	None	N
I/G	0.264	likely_benign	0.3474	ambiguous	-1.978	Destabilizing	0.038	N	0.543	neutral	None	None	None	None	N
I/H	0.2032	likely_benign	0.2536	benign	-1.184	Destabilizing	0.356	N	0.559	neutral	None	None	None	None	N
I/K	0.1571	likely_benign	0.1924	benign	-0.948	Destabilizing	0.038	N	0.583	neutral	None	None	None	None	N
I/L	0.0908	likely_benign	0.0905	benign	-0.692	Destabilizing	None	N	0.091	neutral	N	0.448040975	None	None	N
I/M	0.0809	likely_benign	0.0839	benign	-0.622	Destabilizing	0.093	N	0.458	neutral	N	0.514256809	None	None	N
I/N	0.0761	likely_benign	0.1019	benign	-0.806	Destabilizing	0.029	N	0.606	neutral	N	0.501850618	None	None	N
I/P	0.732	likely_pathogenic	0.855	pathogenic	-0.969	Destabilizing	0.136	N	0.619	neutral	None	None	None	None	N
I/Q	0.1672	likely_benign	0.1997	benign	-0.919	Destabilizing	0.214	N	0.608	neutral	None	None	None	None	N
I/R	0.1212	likely_benign	0.1464	benign	-0.485	Destabilizing	0.214	N	0.613	neutral	None	None	None	None	N
I/S	0.0784	likely_benign	0.1049	benign	-1.539	Destabilizing	0.001	N	0.28	neutral	N	0.451369596	None	None	N
I/T	0.0701	likely_benign	0.0839	benign	-1.372	Destabilizing	None	N	0.183	neutral	N	0.456562538	None	None	N
I/V	0.0557	likely_benign	0.0579	benign	-0.969	Destabilizing	None	N	0.1	neutral	N	0.356362154	None	None	N
I/W	0.6062	likely_pathogenic	0.6882	pathogenic	-1.107	Destabilizing	0.864	D	0.576	neutral	None	None	None	None	N
I/Y	0.2664	likely_benign	0.3358	benign	-0.86	Destabilizing	0.356	N	0.562	neutral	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.