TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33734	101425;101426;101427	chr2:178535415;178535414;178535413	chr2:179400142;179400141;179400140
N2AB	32093	96502;96503;96504	chr2:178535415;178535414;178535413	chr2:179400142;179400141;179400140
N2A	31166	93721;93722;93723	chr2:178535415;178535414;178535413	chr2:179400142;179400141;179400140
N2B	24669	74230;74231;74232	chr2:178535415;178535414;178535413	chr2:179400142;179400141;179400140
Novex-1	24794	74605;74606;74607	chr2:178535415;178535414;178535413	chr2:179400142;179400141;179400140
Novex-2	24861	74806;74807;74808	chr2:178535415;178535414;178535413	chr2:179400142;179400141;179400140
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: Fn3-132
• Domain position: 46
• Structural Position: 63
• Q(SASA): 0.8012
• 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
E/Q	None	None	0.922	N	0.501	0.233	0.195762928549	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	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
E/A	0.4528	ambiguous	0.3069	benign	-0.008	Destabilizing	0.557	D	0.537	neutral	N	0.488737472	None	None	N
E/C	0.9746	likely_pathogenic	0.9438	pathogenic	-0.334	Destabilizing	0.993	D	0.694	prob.neutral	None	None	None	None	N
E/D	0.1756	likely_benign	0.1641	benign	-0.412	Destabilizing	None	N	0.331	neutral	N	0.463937815	None	None	N
E/F	0.9714	likely_pathogenic	0.939	pathogenic	-0.13	Destabilizing	0.996	D	0.623	neutral	None	None	None	None	N
E/G	0.3002	likely_benign	0.195	benign	-0.085	Destabilizing	0.807	D	0.443	neutral	N	0.441615529	None	None	N
E/H	0.871	likely_pathogenic	0.767	pathogenic	0.551	Stabilizing	0.994	D	0.565	neutral	None	None	None	None	N
E/I	0.8875	likely_pathogenic	0.7921	pathogenic	0.134	Stabilizing	0.911	D	0.633	neutral	None	None	None	None	N
E/K	0.491	ambiguous	0.3227	benign	0.239	Stabilizing	0.699	D	0.514	neutral	N	0.446640133	None	None	N
E/L	0.8445	likely_pathogenic	0.7301	pathogenic	0.134	Stabilizing	0.911	D	0.621	neutral	None	None	None	None	N
E/M	0.8864	likely_pathogenic	0.7975	pathogenic	-0.136	Destabilizing	0.955	D	0.599	neutral	None	None	None	None	N
E/N	0.5044	ambiguous	0.3721	ambiguous	0.109	Stabilizing	0.541	D	0.512	neutral	None	None	None	None	N
E/P	0.7615	likely_pathogenic	0.6059	pathogenic	0.102	Stabilizing	0.604	D	0.555	neutral	None	None	None	None	N
E/Q	0.3951	ambiguous	0.2711	benign	0.092	Stabilizing	0.922	D	0.501	neutral	N	0.481136709	None	None	N
E/R	0.6748	likely_pathogenic	0.4898	ambiguous	0.474	Stabilizing	0.956	D	0.551	neutral	None	None	None	None	N
E/S	0.4213	ambiguous	0.2892	benign	-0.051	Destabilizing	0.625	D	0.501	neutral	None	None	None	None	N
E/T	0.5997	likely_pathogenic	0.4355	ambiguous	0.02	Stabilizing	0.89	D	0.534	neutral	None	None	None	None	N
E/V	0.721	likely_pathogenic	0.5725	pathogenic	0.102	Stabilizing	0.846	D	0.573	neutral	N	0.495375443	None	None	N
E/W	0.9888	likely_pathogenic	0.9736	pathogenic	-0.122	Destabilizing	0.999	D	0.7	prob.neutral	None	None	None	None	N
E/Y	0.9434	likely_pathogenic	0.8865	pathogenic	0.076	Stabilizing	0.999	D	0.584	neutral	None	None	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.