TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27291	82096;82097;82098	chr2:178564261;178564260;178564259	chr2:179428988;179428987;179428986
N2AB	25650	77173;77174;77175	chr2:178564261;178564260;178564259	chr2:179428988;179428987;179428986
N2A	24723	74392;74393;74394	chr2:178564261;178564260;178564259	chr2:179428988;179428987;179428986
N2B	18226	54901;54902;54903	chr2:178564261;178564260;178564259	chr2:179428988;179428987;179428986
Novex-1	18351	55276;55277;55278	chr2:178564261;178564260;178564259	chr2:179428988;179428987;179428986
Novex-2	18418	55477;55478;55479	chr2:178564261;178564260;178564259	chr2:179428988;179428987;179428986
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-140
• Domain position: 14
• Structural Position: 25
• Q(SASA): 0.4192
• 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
E/G	rs1197029579	None	0.822	N	0.464	0.305	0.294206760003	gnomAD-4.0.0	1.59247E-06	None	None	None	None	I	None	0	0	None	0	2.77316E-05	None	0	0	0	0	0
E/Q	None	None	0.822	N	0.398	0.272	0.188950314367	gnomAD-4.0.0	2.05333E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79893E-06	1.15931E-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
E/A	0.2558	likely_benign	0.2604	benign	-0.63	Destabilizing	0.822	D	0.399	neutral	N	0.474725103	None	None	I
E/C	0.8798	likely_pathogenic	0.9019	pathogenic	-0.111	Destabilizing	0.998	D	0.691	prob.neutral	None	None	None	None	I
E/D	0.1101	likely_benign	0.109	benign	-0.629	Destabilizing	0.006	N	0.167	neutral	N	0.45141873	None	None	I
E/F	0.8767	likely_pathogenic	0.8947	pathogenic	-0.473	Destabilizing	0.993	D	0.642	neutral	None	None	None	None	I
E/G	0.2217	likely_benign	0.2292	benign	-0.891	Destabilizing	0.822	D	0.464	neutral	N	0.508024161	None	None	I
E/H	0.5652	likely_pathogenic	0.6188	pathogenic	-0.57	Destabilizing	0.993	D	0.365	neutral	None	None	None	None	I
E/I	0.6457	likely_pathogenic	0.6765	pathogenic	0.046	Stabilizing	0.978	D	0.641	neutral	None	None	None	None	I
E/K	0.1871	likely_benign	0.2162	benign	-0.088	Destabilizing	0.822	D	0.394	neutral	N	0.456999242	None	None	I
E/L	0.648	likely_pathogenic	0.6821	pathogenic	0.046	Stabilizing	0.978	D	0.617	neutral	None	None	None	None	I
E/M	0.5736	likely_pathogenic	0.6042	pathogenic	0.392	Stabilizing	0.998	D	0.582	neutral	None	None	None	None	I
E/N	0.2329	likely_benign	0.2386	benign	-0.406	Destabilizing	0.754	D	0.365	neutral	None	None	None	None	I
E/P	0.9754	likely_pathogenic	0.977	pathogenic	-0.158	Destabilizing	0.978	D	0.44	neutral	None	None	None	None	I
E/Q	0.1666	likely_benign	0.1839	benign	-0.338	Destabilizing	0.822	D	0.398	neutral	N	0.515488851	None	None	I
E/R	0.3507	ambiguous	0.4022	ambiguous	0.085	Stabilizing	0.978	D	0.373	neutral	None	None	None	None	I
E/S	0.2242	likely_benign	0.2208	benign	-0.613	Destabilizing	0.754	D	0.362	neutral	None	None	None	None	I
E/T	0.3086	likely_benign	0.3377	benign	-0.404	Destabilizing	0.86	D	0.403	neutral	None	None	None	None	I
E/V	0.4064	ambiguous	0.435	ambiguous	-0.158	Destabilizing	0.971	D	0.483	neutral	N	0.495742647	None	None	I
E/W	0.9586	likely_pathogenic	0.9668	pathogenic	-0.31	Destabilizing	0.998	D	0.693	prob.neutral	None	None	None	None	I
E/Y	0.7541	likely_pathogenic	0.786	pathogenic	-0.243	Destabilizing	0.993	D	0.589	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.