TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30184	90775;90776;90777	chr2:178552350;178552349;178552348	chr2:179417077;179417076;179417075
N2AB	28543	85852;85853;85854	chr2:178552350;178552349;178552348	chr2:179417077;179417076;179417075
N2A	27616	83071;83072;83073	chr2:178552350;178552349;178552348	chr2:179417077;179417076;179417075
N2B	21119	63580;63581;63582	chr2:178552350;178552349;178552348	chr2:179417077;179417076;179417075
Novex-1	21244	63955;63956;63957	chr2:178552350;178552349;178552348	chr2:179417077;179417076;179417075
Novex-2	21311	64156;64157;64158	chr2:178552350;178552349;178552348	chr2:179417077;179417076;179417075
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: Ig-148
• Domain position: 53
• Structural Position: 131
• Q(SASA): 0.5017
• 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/V	rs754965003	-0.015	0.238	N	0.259	0.197	0.366277470483	gnomAD-2.1.1	8.56E-06	None	None	None	None	N	None	0	3.12E-05	None	0	0	None	0	None	0	9.29E-06	0
E/V	rs754965003	-0.015	0.238	N	0.259	0.197	0.366277470483	gnomAD-4.0.0	4.89221E-06	None	None	None	None	N	None	0	2.40223E-05	None	0	0	None	0	0	5.82401E-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	0.1564	likely_benign	0.1377	benign	-0.11	Destabilizing	0.906	D	0.356	neutral	N	0.453592243	None	None	N
E/C	0.8735	likely_pathogenic	0.8549	pathogenic	-0.16	Destabilizing	1.0	D	0.489	neutral	None	None	None	None	N
E/D	0.0984	likely_benign	0.087	benign	-0.27	Destabilizing	0.03	N	0.159	neutral	N	0.436774564	None	None	N
E/F	0.8436	likely_pathogenic	0.8155	pathogenic	-0.138	Destabilizing	0.995	D	0.456	neutral	None	None	None	None	N
E/G	0.155	likely_benign	0.1394	benign	-0.231	Destabilizing	0.979	D	0.375	neutral	N	0.455818898	None	None	N
E/H	0.5562	ambiguous	0.5083	ambiguous	0.423	Stabilizing	0.999	D	0.318	neutral	None	None	None	None	N
E/I	0.4077	ambiguous	0.3753	ambiguous	0.152	Stabilizing	0.939	D	0.4	neutral	None	None	None	None	N
E/K	0.184	likely_benign	0.1659	benign	0.39	Stabilizing	0.979	D	0.342	neutral	N	0.473620799	None	None	N
E/L	0.5071	ambiguous	0.4709	ambiguous	0.152	Stabilizing	0.939	D	0.404	neutral	None	None	None	None	N
E/M	0.5558	ambiguous	0.5187	ambiguous	-0.001	Destabilizing	0.999	D	0.438	neutral	None	None	None	None	N
E/N	0.2353	likely_benign	0.2088	benign	0.158	Stabilizing	0.969	D	0.313	neutral	None	None	None	None	N
E/P	0.3873	ambiguous	0.3378	benign	0.083	Stabilizing	0.999	D	0.319	neutral	None	None	None	None	N
E/Q	0.181	likely_benign	0.1707	benign	0.168	Stabilizing	0.979	D	0.347	neutral	N	0.458248701	None	None	N
E/R	0.3219	likely_benign	0.2957	benign	0.616	Stabilizing	0.995	D	0.323	neutral	None	None	None	None	N
E/S	0.2075	likely_benign	0.181	benign	0.008	Stabilizing	0.969	D	0.312	neutral	None	None	None	None	N
E/T	0.2373	likely_benign	0.2161	benign	0.114	Stabilizing	0.969	D	0.363	neutral	None	None	None	None	N
E/V	0.2656	likely_benign	0.2465	benign	0.083	Stabilizing	0.238	N	0.259	neutral	N	0.477797254	None	None	N
E/W	0.9117	likely_pathogenic	0.8984	pathogenic	-0.075	Destabilizing	1.0	D	0.576	neutral	None	None	None	None	N
E/Y	0.7066	likely_pathogenic	0.6606	pathogenic	0.086	Stabilizing	0.999	D	0.43	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.