TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6735	20428;20429;20430	chr2:178727162;178727161;178727160	chr2:179591889;179591888;179591887
N2AB	6418	19477;19478;19479	chr2:178727162;178727161;178727160	chr2:179591889;179591888;179591887
N2A	5491	16696;16697;16698	chr2:178727162;178727161;178727160	chr2:179591889;179591888;179591887
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Ig-51
• Domain position: 69
• Structural Position: 151
• Q(SASA): 0.2505
• 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/G	None	None	0.002	N	0.159	0.159	0.146414634003	gnomAD-4.0.0	1.59942E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.03656E-05

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	0.1136	likely_benign	0.107	benign	-0.822	Destabilizing	0.008	N	0.463	neutral	None	None	None	None	N
S/C	0.2741	likely_benign	0.2829	benign	-0.585	Destabilizing	0.919	D	0.507	neutral	D	0.535035706	None	None	N
S/D	0.5961	likely_pathogenic	0.6203	pathogenic	-0.018	Destabilizing	0.002	N	0.315	neutral	None	None	None	None	N
S/E	0.7058	likely_pathogenic	0.7229	pathogenic	-0.059	Destabilizing	0.282	N	0.445	neutral	None	None	None	None	N
S/F	0.5663	likely_pathogenic	0.5669	pathogenic	-1.197	Destabilizing	0.937	D	0.575	neutral	None	None	None	None	N
S/G	0.1097	likely_benign	0.1009	benign	-1.001	Destabilizing	0.002	N	0.159	neutral	N	0.489330542	None	None	N
S/H	0.6562	likely_pathogenic	0.6629	pathogenic	-1.469	Destabilizing	0.937	D	0.508	neutral	None	None	None	None	N
S/I	0.4703	ambiguous	0.4729	ambiguous	-0.458	Destabilizing	0.735	D	0.582	neutral	N	0.511816116	None	None	N
S/K	0.8611	likely_pathogenic	0.8807	pathogenic	-0.575	Destabilizing	0.677	D	0.451	neutral	None	None	None	None	N
S/L	0.2313	likely_benign	0.2483	benign	-0.458	Destabilizing	0.512	D	0.541	neutral	None	None	None	None	N
S/M	0.3678	ambiguous	0.3685	ambiguous	-0.102	Destabilizing	0.983	D	0.494	neutral	None	None	None	None	N
S/N	0.2499	likely_benign	0.2512	benign	-0.434	Destabilizing	0.001	N	0.331	neutral	N	0.498293764	None	None	N
S/P	0.8703	likely_pathogenic	0.8786	pathogenic	-0.549	Destabilizing	0.8	D	0.525	neutral	None	None	None	None	N
S/Q	0.7205	likely_pathogenic	0.7247	pathogenic	-0.702	Destabilizing	0.937	D	0.457	neutral	None	None	None	None	N
S/R	0.7805	likely_pathogenic	0.8113	pathogenic	-0.407	Destabilizing	0.847	D	0.53	neutral	N	0.508827149	None	None	N
S/T	0.1052	likely_benign	0.1102	benign	-0.575	Destabilizing	None	N	0.331	neutral	N	0.497485533	None	None	N
S/V	0.4522	ambiguous	0.4492	ambiguous	-0.549	Destabilizing	0.282	N	0.559	neutral	None	None	None	None	N
S/W	0.721	likely_pathogenic	0.7223	pathogenic	-1.091	Destabilizing	0.994	D	0.643	neutral	None	None	None	None	N
S/Y	0.5155	ambiguous	0.505	ambiguous	-0.847	Destabilizing	0.937	D	0.575	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.