TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32031	96316;96317;96318	chr2:178544053;178544052;178544051	chr2:179408780;179408779;179408778
N2AB	30390	91393;91394;91395	chr2:178544053;178544052;178544051	chr2:179408780;179408779;179408778
N2A	29463	88612;88613;88614	chr2:178544053;178544052;178544051	chr2:179408780;179408779;179408778
N2B	22966	69121;69122;69123	chr2:178544053;178544052;178544051	chr2:179408780;179408779;179408778
Novex-1	23091	69496;69497;69498	chr2:178544053;178544052;178544051	chr2:179408780;179408779;179408778
Novex-2	23158	69697;69698;69699	chr2:178544053;178544052;178544051	chr2:179408780;179408779;179408778
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-153
• Domain position: 15
• Structural Position: 26
• Q(SASA): 0.4538
• 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/P	None	None	0.949	N	0.391	0.244	0.212008924253	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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	0.1109	likely_benign	0.1059	benign	-0.578	Destabilizing	0.349	N	0.4	neutral	N	0.514411415	None	None	I
S/C	0.184	likely_benign	0.159	benign	-0.475	Destabilizing	0.995	D	0.437	neutral	N	0.494791141	None	None	I
S/D	0.8388	likely_pathogenic	0.792	pathogenic	0.16	Stabilizing	0.775	D	0.372	neutral	None	None	None	None	I
S/E	0.8894	likely_pathogenic	0.8663	pathogenic	0.157	Stabilizing	0.775	D	0.365	neutral	None	None	None	None	I
S/F	0.5385	ambiguous	0.4707	ambiguous	-0.796	Destabilizing	0.949	D	0.533	neutral	N	0.494537651	None	None	I
S/G	0.176	likely_benign	0.1507	benign	-0.819	Destabilizing	0.775	D	0.407	neutral	None	None	None	None	I
S/H	0.7441	likely_pathogenic	0.688	pathogenic	-1.242	Destabilizing	0.996	D	0.435	neutral	None	None	None	None	I
S/I	0.4021	ambiguous	0.3572	ambiguous	-0.051	Destabilizing	0.858	D	0.463	neutral	None	None	None	None	I
S/K	0.9529	likely_pathogenic	0.9353	pathogenic	-0.524	Destabilizing	0.775	D	0.368	neutral	None	None	None	None	I
S/L	0.2253	likely_benign	0.1986	benign	-0.051	Destabilizing	0.633	D	0.447	neutral	None	None	None	None	I
S/M	0.3337	likely_benign	0.2981	benign	0.055	Stabilizing	0.989	D	0.435	neutral	None	None	None	None	I
S/N	0.3408	ambiguous	0.2931	benign	-0.493	Destabilizing	0.775	D	0.411	neutral	None	None	None	None	I
S/P	0.2734	likely_benign	0.2111	benign	-0.192	Destabilizing	0.949	D	0.391	neutral	N	0.493977428	None	None	I
S/Q	0.8206	likely_pathogenic	0.7838	pathogenic	-0.593	Destabilizing	0.961	D	0.437	neutral	None	None	None	None	I
S/R	0.9392	likely_pathogenic	0.9167	pathogenic	-0.461	Destabilizing	0.923	D	0.397	neutral	None	None	None	None	I
S/T	0.089	likely_benign	0.0847	benign	-0.535	Destabilizing	0.001	N	0.167	neutral	N	0.401816629	None	None	I
S/V	0.3078	likely_benign	0.2763	benign	-0.192	Destabilizing	0.633	D	0.44	neutral	None	None	None	None	I
S/W	0.7616	likely_pathogenic	0.6915	pathogenic	-0.784	Destabilizing	0.996	D	0.625	neutral	None	None	None	None	I
S/Y	0.5061	ambiguous	0.439	ambiguous	-0.497	Destabilizing	0.983	D	0.538	neutral	N	0.483016762	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.