TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28021	84286;84287;84288	chr2:178562071;178562070;178562069	chr2:179426798;179426797;179426796
N2AB	26380	79363;79364;79365	chr2:178562071;178562070;178562069	chr2:179426798;179426797;179426796
N2A	25453	76582;76583;76584	chr2:178562071;178562070;178562069	chr2:179426798;179426797;179426796
N2B	18956	57091;57092;57093	chr2:178562071;178562070;178562069	chr2:179426798;179426797;179426796
Novex-1	19081	57466;57467;57468	chr2:178562071;178562070;178562069	chr2:179426798;179426797;179426796
Novex-2	19148	57667;57668;57669	chr2:178562071;178562070;178562069	chr2:179426798;179426797;179426796
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-142
• Domain position: 59
• Structural Position: 139
• Q(SASA): 0.3454
• 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/C	None	None	0.196	N	0.453	0.095	0.209622950755	gnomAD-4.0.0	1.59246E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43357E-05	0
S/P	None	None	0.065	N	0.493	0.144	0.0666544352282	gnomAD-4.0.0	1.20034E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31252E-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	0.083	likely_benign	0.0817	benign	-0.781	Destabilizing	None	N	0.154	neutral	N	0.478531626	None	None	N
S/C	0.0714	likely_benign	0.0772	benign	-0.886	Destabilizing	0.196	N	0.453	neutral	N	0.479745134	None	None	N
S/D	0.3246	likely_benign	0.3612	ambiguous	-1.23	Destabilizing	0.044	N	0.383	neutral	None	None	None	None	N
S/E	0.3831	ambiguous	0.4431	ambiguous	-1.125	Destabilizing	0.018	N	0.373	neutral	None	None	None	None	N
S/F	0.0909	likely_benign	0.101	benign	-0.707	Destabilizing	0.033	N	0.514	neutral	N	0.434530133	None	None	N
S/G	0.1218	likely_benign	0.1294	benign	-1.113	Destabilizing	0.009	N	0.317	neutral	None	None	None	None	N
S/H	0.1708	likely_benign	0.1921	benign	-1.519	Destabilizing	0.497	N	0.451	neutral	None	None	None	None	N
S/I	0.0634	likely_benign	0.076	benign	0.022	Stabilizing	None	N	0.303	neutral	None	None	None	None	N
S/K	0.5141	ambiguous	0.5975	pathogenic	-0.734	Destabilizing	0.018	N	0.366	neutral	None	None	None	None	N
S/L	0.0638	likely_benign	0.0684	benign	0.022	Stabilizing	None	N	0.293	neutral	None	None	None	None	N
S/M	0.0995	likely_benign	0.1086	benign	0.04	Stabilizing	0.138	N	0.497	neutral	None	None	None	None	N
S/N	0.0834	likely_benign	0.0882	benign	-1.131	Destabilizing	0.044	N	0.425	neutral	None	None	None	None	N
S/P	0.8715	likely_pathogenic	0.8985	pathogenic	-0.21	Destabilizing	0.065	N	0.493	neutral	N	0.50920125	None	None	N
S/Q	0.3169	likely_benign	0.3482	ambiguous	-1.112	Destabilizing	0.085	N	0.435	neutral	None	None	None	None	N
S/R	0.4122	ambiguous	0.5079	ambiguous	-0.815	Destabilizing	0.044	N	0.52	neutral	None	None	None	None	N
S/T	0.0591	likely_benign	0.0569	benign	-0.92	Destabilizing	None	N	0.154	neutral	N	0.394064803	None	None	N
S/V	0.0858	likely_benign	0.0912	benign	-0.21	Destabilizing	None	N	0.298	neutral	None	None	None	None	N
S/W	0.1831	likely_benign	0.2204	benign	-0.819	Destabilizing	0.788	D	0.525	neutral	None	None	None	None	N
S/Y	0.1066	likely_benign	0.1178	benign	-0.462	Destabilizing	0.065	N	0.566	neutral	N	0.456502915	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.