TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7334	22225;22226;22227	chr2:178722899;178722898;178722897	chr2:179587626;179587625;179587624
N2AB	7017	21274;21275;21276	chr2:178722899;178722898;178722897	chr2:179587626;179587625;179587624
N2A	6090	18493;18494;18495	chr2:178722899;178722898;178722897	chr2:179587626;179587625;179587624
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: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-58
• Domain position: 12
• Structural Position: 16
• Q(SASA): 0.5656
• 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
A/V	None	None	0.095	N	0.215	0.112	0.257292322809	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
A/C	0.5384	ambiguous	0.6054	pathogenic	-0.906	Destabilizing	1.0	D	0.377	neutral	None	None	None	None	I
A/D	0.4654	ambiguous	0.6289	pathogenic	-1.681	Destabilizing	0.99	D	0.41	neutral	None	None	None	None	I
A/E	0.4014	ambiguous	0.525	ambiguous	-1.581	Destabilizing	0.999	D	0.409	neutral	N	0.501789711	None	None	I
A/F	0.3897	ambiguous	0.5043	ambiguous	-0.819	Destabilizing	0.999	D	0.395	neutral	None	None	None	None	I
A/G	0.1436	likely_benign	0.1835	benign	-1.373	Destabilizing	0.683	D	0.325	neutral	N	0.495775776	None	None	I
A/H	0.6433	likely_pathogenic	0.7535	pathogenic	-1.72	Destabilizing	1.0	D	0.387	neutral	None	None	None	None	I
A/I	0.211	likely_benign	0.2952	benign	0.025	Stabilizing	0.993	D	0.361	neutral	None	None	None	None	I
A/K	0.5429	ambiguous	0.6772	pathogenic	-1.244	Destabilizing	1.0	D	0.411	neutral	None	None	None	None	I
A/L	0.2189	likely_benign	0.3036	benign	0.025	Stabilizing	0.983	D	0.33	neutral	None	None	None	None	I
A/M	0.2164	likely_benign	0.2929	benign	-0.033	Destabilizing	1.0	D	0.379	neutral	None	None	None	None	I
A/N	0.4092	ambiguous	0.5616	ambiguous	-1.219	Destabilizing	0.923	D	0.4	neutral	None	None	None	None	I
A/P	0.6894	likely_pathogenic	0.8146	pathogenic	-0.263	Destabilizing	0.994	D	0.397	neutral	N	0.516032852	None	None	I
A/Q	0.522	ambiguous	0.6236	pathogenic	-1.184	Destabilizing	0.999	D	0.383	neutral	None	None	None	None	I
A/R	0.5263	ambiguous	0.6325	pathogenic	-1.131	Destabilizing	1.0	D	0.391	neutral	None	None	None	None	I
A/S	0.1306	likely_benign	0.1589	benign	-1.628	Destabilizing	0.06	N	0.269	neutral	N	0.512801702	None	None	I
A/T	0.0936	likely_benign	0.1137	benign	-1.409	Destabilizing	0.076	N	0.203	neutral	D	0.523690699	None	None	I
A/V	0.095	likely_benign	0.1205	benign	-0.263	Destabilizing	0.095	N	0.215	neutral	N	0.41896046	None	None	I
A/W	0.8219	likely_pathogenic	0.8853	pathogenic	-1.429	Destabilizing	1.0	D	0.523	neutral	None	None	None	None	I
A/Y	0.5429	ambiguous	0.6679	pathogenic	-0.892	Destabilizing	1.0	D	0.393	neutral	None	None	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.