TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14113	42562;42563;42564	chr2:178634444;178634443;178634442	chr2:179499171;179499170;179499169
N2AB	12472	37639;37640;37641	chr2:178634444;178634443;178634442	chr2:179499171;179499170;179499169
N2A	11545	34858;34859;34860	chr2:178634444;178634443;178634442	chr2:179499171;179499170;179499169
N2B	5048	15367;15368;15369	chr2:178634444;178634443;178634442	chr2:179499171;179499170;179499169
Novex-1	5173	15742;15743;15744	chr2:178634444;178634443;178634442	chr2:179499171;179499170;179499169
Novex-2	5240	15943;15944;15945	chr2:178634444;178634443;178634442	chr2:179499171;179499170;179499169
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-91
• Domain position: 60
• Structural Position: 143
• Q(SASA): 0.6454
• 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
D/E	None	None	0.012	N	0.277	0.069	0.101711395817	gnomAD-4.0.0	1.59261E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86046E-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
D/A	0.3446	ambiguous	0.2566	benign	-0.092	Destabilizing	0.012	N	0.357	neutral	N	0.441336854	None	None	N
D/C	0.7804	likely_pathogenic	0.6143	pathogenic	0.143	Stabilizing	None	N	0.244	neutral	None	None	None	None	N
D/E	0.2756	likely_benign	0.2433	benign	-0.573	Destabilizing	0.012	N	0.277	neutral	N	0.453534179	None	None	N
D/F	0.7643	likely_pathogenic	0.6509	pathogenic	-0.431	Destabilizing	0.356	N	0.486	neutral	None	None	None	None	N
D/G	0.2725	likely_benign	0.1961	benign	-0.335	Destabilizing	0.012	N	0.298	neutral	N	0.454835669	None	None	N
D/H	0.3667	ambiguous	0.2493	benign	-0.826	Destabilizing	None	N	0.171	neutral	N	0.460084552	None	None	N
D/I	0.7379	likely_pathogenic	0.6444	pathogenic	0.505	Stabilizing	0.356	N	0.493	neutral	None	None	None	None	N
D/K	0.5548	ambiguous	0.39	ambiguous	-0.105	Destabilizing	0.038	N	0.335	neutral	None	None	None	None	N
D/L	0.6714	likely_pathogenic	0.5608	ambiguous	0.505	Stabilizing	0.072	N	0.443	neutral	None	None	None	None	N
D/M	0.8384	likely_pathogenic	0.781	pathogenic	0.912	Stabilizing	0.864	D	0.446	neutral	None	None	None	None	N
D/N	0.0924	likely_benign	0.0741	benign	-0.245	Destabilizing	None	N	0.085	neutral	N	0.425413419	None	None	N
D/P	0.9665	likely_pathogenic	0.9483	pathogenic	0.331	Stabilizing	0.356	N	0.412	neutral	None	None	None	None	N
D/Q	0.4713	ambiguous	0.3862	ambiguous	-0.184	Destabilizing	0.214	N	0.326	neutral	None	None	None	None	N
D/R	0.5316	ambiguous	0.3987	ambiguous	-0.187	Destabilizing	0.214	N	0.466	neutral	None	None	None	None	N
D/S	0.1741	likely_benign	0.126	benign	-0.405	Destabilizing	0.003	N	0.176	neutral	None	None	None	None	N
D/T	0.4883	ambiguous	0.3793	ambiguous	-0.225	Destabilizing	0.038	N	0.307	neutral	None	None	None	None	N
D/V	0.58	likely_pathogenic	0.4927	ambiguous	0.331	Stabilizing	0.055	N	0.473	neutral	D	0.581268067	None	None	N
D/W	0.9471	likely_pathogenic	0.9147	pathogenic	-0.528	Destabilizing	0.864	D	0.499	neutral	None	None	None	None	N
D/Y	0.3361	likely_benign	0.2288	benign	-0.274	Destabilizing	0.093	N	0.507	neutral	D	0.581106766	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.