TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29848	89767;89768;89769	chr2:178553358;178553357;178553356	chr2:179418085;179418084;179418083
N2AB	28207	84844;84845;84846	chr2:178553358;178553357;178553356	chr2:179418085;179418084;179418083
N2A	27280	82063;82064;82065	chr2:178553358;178553357;178553356	chr2:179418085;179418084;179418083
N2B	20783	62572;62573;62574	chr2:178553358;178553357;178553356	chr2:179418085;179418084;179418083
Novex-1	20908	62947;62948;62949	chr2:178553358;178553357;178553356	chr2:179418085;179418084;179418083
Novex-2	20975	63148;63149;63150	chr2:178553358;178553357;178553356	chr2:179418085;179418084;179418083
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-147
• Domain position: 7
• Structural Position: 11
• Q(SASA): 0.5204
• 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
S/T	None	None	0.98	N	0.421	0.176	0.132336055621	gnomAD-4.0.0	2.40065E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.62501E-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
S/A	0.0939	likely_benign	0.0849	benign	-0.616	Destabilizing	0.91	D	0.371	neutral	N	0.42015446	None	None	I
S/C	0.1427	likely_benign	0.1316	benign	-0.368	Destabilizing	1.0	D	0.494	neutral	N	0.498231242	None	None	I
S/D	0.6322	likely_pathogenic	0.5964	pathogenic	0.33	Stabilizing	0.97	D	0.345	neutral	None	None	None	None	I
S/E	0.6519	likely_pathogenic	0.636	pathogenic	0.251	Stabilizing	0.871	D	0.38	neutral	None	None	None	None	I
S/F	0.3261	likely_benign	0.2669	benign	-1.171	Destabilizing	0.998	D	0.552	neutral	N	0.483704506	None	None	I
S/G	0.124	likely_benign	0.1131	benign	-0.743	Destabilizing	0.965	D	0.368	neutral	None	None	None	None	I
S/H	0.4033	ambiguous	0.3983	ambiguous	-1.329	Destabilizing	0.996	D	0.461	neutral	None	None	None	None	I
S/I	0.2619	likely_benign	0.2169	benign	-0.405	Destabilizing	0.999	D	0.534	neutral	None	None	None	None	I
S/K	0.7818	likely_pathogenic	0.7791	pathogenic	-0.453	Destabilizing	0.942	D	0.361	neutral	None	None	None	None	I
S/L	0.1619	likely_benign	0.1341	benign	-0.405	Destabilizing	0.97	D	0.477	neutral	None	None	None	None	I
S/M	0.2428	likely_benign	0.2077	benign	-0.057	Destabilizing	0.999	D	0.459	neutral	None	None	None	None	I
S/N	0.1876	likely_benign	0.1747	benign	-0.193	Destabilizing	0.985	D	0.407	neutral	None	None	None	None	I
S/P	0.7508	likely_pathogenic	0.6718	pathogenic	-0.447	Destabilizing	0.998	D	0.421	neutral	N	0.426560357	None	None	I
S/Q	0.5505	ambiguous	0.5423	ambiguous	-0.446	Destabilizing	0.559	D	0.187	neutral	None	None	None	None	I
S/R	0.7	likely_pathogenic	0.6978	pathogenic	-0.344	Destabilizing	0.97	D	0.426	neutral	None	None	None	None	I
S/T	0.0856	likely_benign	0.0759	benign	-0.345	Destabilizing	0.98	D	0.421	neutral	N	0.355796337	None	None	I
S/V	0.2185	likely_benign	0.1847	benign	-0.447	Destabilizing	0.985	D	0.493	neutral	None	None	None	None	I
S/W	0.4612	ambiguous	0.4116	ambiguous	-1.114	Destabilizing	1.0	D	0.657	neutral	None	None	None	None	I
S/Y	0.2619	likely_benign	0.2309	benign	-0.852	Destabilizing	0.998	D	0.543	neutral	N	0.497884525	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.