TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29494	88705;88706;88707	chr2:178554979;178554978;178554977	chr2:179419706;179419705;179419704
N2AB	27853	83782;83783;83784	chr2:178554979;178554978;178554977	chr2:179419706;179419705;179419704
N2A	26926	81001;81002;81003	chr2:178554979;178554978;178554977	chr2:179419706;179419705;179419704
N2B	20429	61510;61511;61512	chr2:178554979;178554978;178554977	chr2:179419706;179419705;179419704
Novex-1	20554	61885;61886;61887	chr2:178554979;178554978;178554977	chr2:179419706;179419705;179419704
Novex-2	20621	62086;62087;62088	chr2:178554979;178554978;178554977	chr2:179419706;179419705;179419704
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-146
• Domain position: 51
• Structural Position: 134
• Q(SASA): 0.6529
• 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
D/E	None	None	0.003	N	0.173	0.141	0.241664281697	gnomAD-4.0.0	6.84269E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15939E-05	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
D/A	0.1925	likely_benign	0.1844	benign	-0.266	Destabilizing	0.565	D	0.55	neutral	N	0.517511302	None	None	N
D/C	0.623	likely_pathogenic	0.6061	pathogenic	0.096	Stabilizing	0.996	D	0.702	prob.neutral	None	None	None	None	N
D/E	0.1436	likely_benign	0.1507	benign	-0.202	Destabilizing	0.003	N	0.173	neutral	N	0.45886843	None	None	N
D/F	0.6243	likely_pathogenic	0.5935	pathogenic	-0.267	Destabilizing	0.987	D	0.651	neutral	None	None	None	None	N
D/G	0.1741	likely_benign	0.1663	benign	-0.419	Destabilizing	0.722	D	0.492	neutral	N	0.478723627	None	None	N
D/H	0.2805	likely_benign	0.2663	benign	0.004	Stabilizing	0.949	D	0.567	neutral	N	0.484935996	None	None	N
D/I	0.4108	ambiguous	0.3916	ambiguous	0.084	Stabilizing	0.961	D	0.652	neutral	None	None	None	None	N
D/K	0.3903	ambiguous	0.3885	ambiguous	0.512	Stabilizing	0.633	D	0.49	neutral	None	None	None	None	N
D/L	0.4105	ambiguous	0.3865	ambiguous	0.084	Stabilizing	0.923	D	0.599	neutral	None	None	None	None	N
D/M	0.6088	likely_pathogenic	0.5884	pathogenic	0.193	Stabilizing	0.996	D	0.651	neutral	None	None	None	None	N
D/N	0.1119	likely_benign	0.1024	benign	0.179	Stabilizing	0.722	D	0.495	neutral	N	0.433991415	None	None	N
D/P	0.7839	likely_pathogenic	0.7952	pathogenic	-0.013	Destabilizing	0.961	D	0.541	neutral	None	None	None	None	N
D/Q	0.3151	likely_benign	0.3156	benign	0.203	Stabilizing	0.237	N	0.173	neutral	None	None	None	None	N
D/R	0.4251	ambiguous	0.4223	ambiguous	0.611	Stabilizing	0.923	D	0.582	neutral	None	None	None	None	N
D/S	0.1311	likely_benign	0.124	benign	0.11	Stabilizing	0.633	D	0.416	neutral	None	None	None	None	N
D/T	0.2186	likely_benign	0.2038	benign	0.237	Stabilizing	0.775	D	0.544	neutral	None	None	None	None	N
D/V	0.2426	likely_benign	0.2335	benign	-0.013	Destabilizing	0.901	D	0.599	neutral	N	0.484429017	None	None	N
D/W	0.8662	likely_pathogenic	0.8589	pathogenic	-0.151	Destabilizing	0.996	D	0.695	prob.neutral	None	None	None	None	N
D/Y	0.2454	likely_benign	0.2291	benign	-0.032	Destabilizing	0.983	D	0.651	neutral	N	0.497773535	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.