TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33249	99970;99971;99972	chr2:178537462;178537461;178537460	chr2:179402189;179402188;179402187
N2AB	31608	95047;95048;95049	chr2:178537462;178537461;178537460	chr2:179402189;179402188;179402187
N2A	30681	92266;92267;92268	chr2:178537462;178537461;178537460	chr2:179402189;179402188;179402187
N2B	24184	72775;72776;72777	chr2:178537462;178537461;178537460	chr2:179402189;179402188;179402187
Novex-1	24309	73150;73151;73152	chr2:178537462;178537461;178537460	chr2:179402189;179402188;179402187
Novex-2	24376	73351;73352;73353	chr2:178537462;178537461;178537460	chr2:179402189;179402188;179402187
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-157
• Domain position: 47
• Structural Position: 131
• Q(SASA): 0.2721
• 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/K	None	None	0.999	N	0.557	0.38	0.223847106136	gnomAD-4.0.0	1.36878E-06	None	None	None	None	N	None	0	0	None	0	5.04541E-05	None	0	0	0	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	0.3538	ambiguous	0.3614	ambiguous	-0.516	Destabilizing	0.998	D	0.627	neutral	N	0.475679669	None	None	N
E/C	0.9774	likely_pathogenic	0.9748	pathogenic	-0.347	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
E/D	0.2649	likely_benign	0.2587	benign	-0.427	Destabilizing	0.074	N	0.289	neutral	N	0.430040593	None	None	N
E/F	0.9649	likely_pathogenic	0.9629	pathogenic	-0.217	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
E/G	0.3849	ambiguous	0.3995	ambiguous	-0.749	Destabilizing	1.0	D	0.591	neutral	N	0.464438381	None	None	N
E/H	0.8632	likely_pathogenic	0.8572	pathogenic	0.064	Stabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
E/I	0.7663	likely_pathogenic	0.7827	pathogenic	0.08	Stabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	N
E/K	0.3739	ambiguous	0.391	ambiguous	-0.122	Destabilizing	0.999	D	0.557	neutral	N	0.475506311	None	None	N
E/L	0.8027	likely_pathogenic	0.8044	pathogenic	0.08	Stabilizing	1.0	D	0.692	prob.neutral	None	None	None	None	N
E/M	0.8427	likely_pathogenic	0.8448	pathogenic	0.09	Stabilizing	1.0	D	0.692	prob.neutral	None	None	None	None	N
E/N	0.6202	likely_pathogenic	0.6173	pathogenic	-0.397	Destabilizing	0.997	D	0.69	prob.neutral	None	None	None	None	N
E/P	0.6425	likely_pathogenic	0.6023	pathogenic	-0.099	Destabilizing	0.999	D	0.679	prob.neutral	None	None	None	None	N
E/Q	0.3656	ambiguous	0.3739	ambiguous	-0.334	Destabilizing	0.999	D	0.638	neutral	N	0.491110481	None	None	N
E/R	0.5712	likely_pathogenic	0.5668	pathogenic	0.263	Stabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
E/S	0.4372	ambiguous	0.435	ambiguous	-0.624	Destabilizing	0.996	D	0.591	neutral	None	None	None	None	N
E/T	0.5668	likely_pathogenic	0.5835	pathogenic	-0.438	Destabilizing	1.0	D	0.662	neutral	None	None	None	None	N
E/V	0.5868	likely_pathogenic	0.6103	pathogenic	-0.099	Destabilizing	1.0	D	0.655	neutral	N	0.510389675	None	None	N
E/W	0.9864	likely_pathogenic	0.9848	pathogenic	-0.029	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
E/Y	0.9311	likely_pathogenic	0.9272	pathogenic	0.016	Stabilizing	1.0	D	0.693	prob.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.