TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24477	73654;73655;73656	chr2:178572703;178572702;178572701	chr2:179437430;179437429;179437428
N2AB	22836	68731;68732;68733	chr2:178572703;178572702;178572701	chr2:179437430;179437429;179437428
N2A	21909	65950;65951;65952	chr2:178572703;178572702;178572701	chr2:179437430;179437429;179437428
N2B	15412	46459;46460;46461	chr2:178572703;178572702;178572701	chr2:179437430;179437429;179437428
Novex-1	15537	46834;46835;46836	chr2:178572703;178572702;178572701	chr2:179437430;179437429;179437428
Novex-2	15604	47035;47036;47037	chr2:178572703;178572702;178572701	chr2:179437430;179437429;179437428
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCC
• RefSeq wild type template codon: AGG
• Domain: Ig-132
• Domain position: 47
• Structural Position: 127
• Q(SASA): 0.6025
• 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/F	None	None	0.003	N	0.473	0.142	0.436671004673	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	None	0	0	0	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	0.089	likely_benign	0.1022	benign	-0.506	Destabilizing	0.285	N	0.346	neutral	D	0.530536527	None	None	N
S/C	0.1098	likely_benign	0.1111	benign	-0.328	Destabilizing	0.987	D	0.49	neutral	N	0.491822076	None	None	N
S/D	0.4871	ambiguous	0.5146	ambiguous	0.296	Stabilizing	0.39	N	0.357	neutral	None	None	None	None	N
S/E	0.57	likely_pathogenic	0.6019	pathogenic	0.249	Stabilizing	0.561	D	0.357	neutral	None	None	None	None	N
S/F	0.308	likely_benign	0.3875	ambiguous	-0.835	Destabilizing	0.003	N	0.473	neutral	N	0.488209902	None	None	N
S/G	0.1264	likely_benign	0.1367	benign	-0.698	Destabilizing	0.345	N	0.343	neutral	None	None	None	None	N
S/H	0.3958	ambiguous	0.4086	ambiguous	-1.166	Destabilizing	0.901	D	0.499	neutral	None	None	None	None	N
S/I	0.1336	likely_benign	0.1537	benign	-0.119	Destabilizing	0.007	N	0.403	neutral	None	None	None	None	N
S/K	0.6631	likely_pathogenic	0.6983	pathogenic	-0.518	Destabilizing	0.561	D	0.354	neutral	None	None	None	None	N
S/L	0.1324	likely_benign	0.1582	benign	-0.119	Destabilizing	0.209	N	0.568	neutral	None	None	None	None	N
S/M	0.1687	likely_benign	0.1884	benign	0.046	Stabilizing	0.901	D	0.502	neutral	None	None	None	None	N
S/N	0.098	likely_benign	0.1028	benign	-0.317	Destabilizing	0.017	N	0.264	neutral	None	None	None	None	N
S/P	0.6763	likely_pathogenic	0.7054	pathogenic	-0.215	Destabilizing	0.954	D	0.503	neutral	N	0.49482923	None	None	N
S/Q	0.5166	ambiguous	0.5354	ambiguous	-0.489	Destabilizing	0.901	D	0.471	neutral	None	None	None	None	N
S/R	0.6706	likely_pathogenic	0.7082	pathogenic	-0.395	Destabilizing	0.901	D	0.497	neutral	None	None	None	None	N
S/T	0.0626	likely_benign	0.0654	benign	-0.407	Destabilizing	0.013	N	0.255	neutral	N	0.399148123	None	None	N
S/V	0.1344	likely_benign	0.1515	benign	-0.215	Destabilizing	0.209	N	0.561	neutral	None	None	None	None	N
S/W	0.5248	ambiguous	0.5783	pathogenic	-0.817	Destabilizing	0.991	D	0.591	neutral	None	None	None	None	N
S/Y	0.2375	likely_benign	0.2798	benign	-0.55	Destabilizing	0.629	D	0.559	neutral	N	0.506275588	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.