TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26762	80509;80510;80511	chr2:178565848;178565847;178565846	chr2:179430575;179430574;179430573
N2AB	25121	75586;75587;75588	chr2:178565848;178565847;178565846	chr2:179430575;179430574;179430573
N2A	24194	72805;72806;72807	chr2:178565848;178565847;178565846	chr2:179430575;179430574;179430573
N2B	17697	53314;53315;53316	chr2:178565848;178565847;178565846	chr2:179430575;179430574;179430573
Novex-1	17822	53689;53690;53691	chr2:178565848;178565847;178565846	chr2:179430575;179430574;179430573
Novex-2	17889	53890;53891;53892	chr2:178565848;178565847;178565846	chr2:179430575;179430574;179430573
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-82
• Domain position: 80
• Structural Position: 113
• Q(SASA): 0.5206
• 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/K	None	None	0.763	N	0.507	0.32	0.247872288689	gnomAD-4.0.0	1.59164E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85922E-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
E/A	0.4336	ambiguous	0.505	ambiguous	-0.556	Destabilizing	0.777	D	0.571	neutral	N	0.513168983	None	None	I
E/C	0.9616	likely_pathogenic	0.9711	pathogenic	-0.267	Destabilizing	0.997	D	0.745	deleterious	None	None	None	None	I
E/D	0.2437	likely_benign	0.2653	benign	-0.449	Destabilizing	0.31	N	0.385	neutral	N	0.472254157	None	None	I
E/F	0.9732	likely_pathogenic	0.9793	pathogenic	-0.188	Destabilizing	0.999	D	0.675	neutral	None	None	None	None	I
E/G	0.693	likely_pathogenic	0.7517	pathogenic	-0.776	Destabilizing	0.976	D	0.551	neutral	N	0.474804463	None	None	I
E/H	0.8792	likely_pathogenic	0.9109	pathogenic	0.188	Stabilizing	0.994	D	0.685	prob.neutral	None	None	None	None	I
E/I	0.601	likely_pathogenic	0.6529	pathogenic	0.006	Stabilizing	0.966	D	0.681	prob.neutral	None	None	None	None	I
E/K	0.5419	ambiguous	0.6203	pathogenic	0.278	Stabilizing	0.763	D	0.507	neutral	N	0.495103297	None	None	I
E/L	0.8254	likely_pathogenic	0.8572	pathogenic	0.006	Stabilizing	0.933	D	0.637	neutral	None	None	None	None	I
E/M	0.7985	likely_pathogenic	0.8337	pathogenic	0.057	Stabilizing	0.95	D	0.675	prob.neutral	None	None	None	None	I
E/N	0.6204	likely_pathogenic	0.6831	pathogenic	-0.299	Destabilizing	0.867	D	0.679	prob.neutral	None	None	None	None	I
E/P	0.8905	likely_pathogenic	0.9032	pathogenic	-0.162	Destabilizing	0.809	D	0.656	neutral	None	None	None	None	I
E/Q	0.3801	ambiguous	0.4333	ambiguous	-0.225	Destabilizing	0.125	N	0.342	neutral	N	0.470038885	None	None	I
E/R	0.7039	likely_pathogenic	0.758	pathogenic	0.605	Stabilizing	0.937	D	0.673	neutral	None	None	None	None	I
E/S	0.55	ambiguous	0.6216	pathogenic	-0.428	Destabilizing	0.822	D	0.597	neutral	None	None	None	None	I
E/T	0.555	ambiguous	0.6369	pathogenic	-0.23	Destabilizing	0.957	D	0.627	neutral	None	None	None	None	I
E/V	0.4862	ambiguous	0.5384	ambiguous	-0.162	Destabilizing	0.882	D	0.643	neutral	N	0.476800061	None	None	I
E/W	0.994	likely_pathogenic	0.9959	pathogenic	0.07	Stabilizing	0.999	D	0.745	deleterious	None	None	None	None	I
E/Y	0.9263	likely_pathogenic	0.9434	pathogenic	0.085	Stabilizing	0.998	D	0.683	prob.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.