TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14813	44662;44663;44664	chr2:178625384;178625383;178625382	chr2:179490111;179490110;179490109
N2AB	13172	39739;39740;39741	chr2:178625384;178625383;178625382	chr2:179490111;179490110;179490109
N2A	12245	36958;36959;36960	chr2:178625384;178625383;178625382	chr2:179490111;179490110;179490109
N2B	5748	17467;17468;17469	chr2:178625384;178625383;178625382	chr2:179490111;179490110;179490109
Novex-1	5873	17842;17843;17844	chr2:178625384;178625383;178625382	chr2:179490111;179490110;179490109
Novex-2	5940	18043;18044;18045	chr2:178625384;178625383;178625382	chr2:179490111;179490110;179490109
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Ig-99
• Domain position: 49
• Structural Position: 127
• Q(SASA): 0.5069
• 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
S/T	None	None	0.625	N	0.399	0.113	0.209622950755	gnomAD-4.0.0	1.68559E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.96813E-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	0.0715	likely_benign	0.068	benign	-0.469	Destabilizing	0.002	N	0.233	neutral	N	0.427433977	None	None	N
S/C	0.1149	likely_benign	0.1116	benign	-0.237	Destabilizing	0.974	D	0.458	neutral	None	None	None	None	N
S/D	0.4662	ambiguous	0.543	ambiguous	-0.136	Destabilizing	0.915	D	0.451	neutral	None	None	None	None	N
S/E	0.507	ambiguous	0.566	pathogenic	-0.216	Destabilizing	0.842	D	0.397	neutral	None	None	None	None	N
S/F	0.2312	likely_benign	0.2231	benign	-0.941	Destabilizing	0.974	D	0.56	neutral	None	None	None	None	N
S/G	0.1089	likely_benign	0.1183	benign	-0.619	Destabilizing	0.525	D	0.411	neutral	None	None	None	None	N
S/H	0.3383	likely_benign	0.3536	ambiguous	-1.178	Destabilizing	0.998	D	0.457	neutral	None	None	None	None	N
S/I	0.1717	likely_benign	0.1769	benign	-0.197	Destabilizing	0.728	D	0.511	neutral	None	None	None	None	N
S/K	0.5441	ambiguous	0.559	ambiguous	-0.626	Destabilizing	0.842	D	0.395	neutral	None	None	None	None	N
S/L	0.1195	likely_benign	0.1142	benign	-0.197	Destabilizing	0.454	N	0.517	neutral	N	0.512093164	None	None	N
S/M	0.2193	likely_benign	0.2154	benign	0.183	Stabilizing	0.974	D	0.465	neutral	None	None	None	None	N
S/N	0.1657	likely_benign	0.1945	benign	-0.32	Destabilizing	0.915	D	0.48	neutral	None	None	None	None	N
S/P	0.3242	likely_benign	0.3617	ambiguous	-0.257	Destabilizing	0.966	D	0.456	neutral	N	0.513531673	None	None	N
S/Q	0.4491	ambiguous	0.4588	ambiguous	-0.604	Destabilizing	0.974	D	0.479	neutral	None	None	None	None	N
S/R	0.4303	ambiguous	0.4529	ambiguous	-0.397	Destabilizing	0.974	D	0.467	neutral	None	None	None	None	N
S/T	0.0914	likely_benign	0.0925	benign	-0.4	Destabilizing	0.625	D	0.399	neutral	N	0.488187177	None	None	N
S/V	0.1651	likely_benign	0.1625	benign	-0.257	Destabilizing	0.067	N	0.39	neutral	None	None	None	None	N
S/W	0.3155	likely_benign	0.3255	benign	-0.923	Destabilizing	0.998	D	0.605	neutral	None	None	None	None	N
S/Y	0.1813	likely_benign	0.1909	benign	-0.667	Destabilizing	0.991	D	0.551	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.