TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31875	95848;95849;95850	chr2:178545487;178545486;178545485	chr2:179410214;179410213;179410212
N2AB	30234	90925;90926;90927	chr2:178545487;178545486;178545485	chr2:179410214;179410213;179410212
N2A	29307	88144;88145;88146	chr2:178545487;178545486;178545485	chr2:179410214;179410213;179410212
N2B	22810	68653;68654;68655	chr2:178545487;178545486;178545485	chr2:179410214;179410213;179410212
Novex-1	22935	69028;69029;69030	chr2:178545487;178545486;178545485	chr2:179410214;179410213;179410212
Novex-2	23002	69229;69230;69231	chr2:178545487;178545486;178545485	chr2:179410214;179410213;179410212
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: Fn3-120
• Domain position: 69
• Structural Position: 99
• Q(SASA): 0.4827
• 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	rs371534086	None	0.999	N	0.695	0.433	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
E/K	rs371534086	None	0.999	N	0.695	0.433	None	gnomAD-4.0.0	1.85935E-06	None	None	None	None	N	None	2.67008E-05	0	None	0	0	None	0	0	0	0	1.60128E-05

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	0.2701	likely_benign	0.2121	benign	-0.429	Destabilizing	0.999	D	0.653	neutral	N	0.496586156	None	None	N
E/C	0.9477	likely_pathogenic	0.9318	pathogenic	0.02	Stabilizing	1.0	D	0.652	neutral	None	None	None	None	N
E/D	0.3331	likely_benign	0.2783	benign	-0.449	Destabilizing	0.999	D	0.579	neutral	N	0.490259961	None	None	N
E/F	0.9554	likely_pathogenic	0.9353	pathogenic	-0.434	Destabilizing	1.0	D	0.62	neutral	None	None	None	None	N
E/G	0.4677	ambiguous	0.3843	ambiguous	-0.642	Destabilizing	1.0	D	0.61	neutral	N	0.517011497	None	None	N
E/H	0.8181	likely_pathogenic	0.7729	pathogenic	-0.434	Destabilizing	1.0	D	0.625	neutral	None	None	None	None	N
E/I	0.6749	likely_pathogenic	0.578	pathogenic	0.101	Stabilizing	1.0	D	0.635	neutral	None	None	None	None	N
E/K	0.4155	ambiguous	0.3487	ambiguous	0.133	Stabilizing	0.999	D	0.695	prob.neutral	N	0.497639794	None	None	N
E/L	0.7492	likely_pathogenic	0.6558	pathogenic	0.101	Stabilizing	1.0	D	0.631	neutral	None	None	None	None	N
E/M	0.7746	likely_pathogenic	0.7042	pathogenic	0.34	Stabilizing	1.0	D	0.591	neutral	None	None	None	None	N
E/N	0.5735	likely_pathogenic	0.499	ambiguous	-0.047	Destabilizing	1.0	D	0.684	prob.neutral	None	None	None	None	N
E/P	0.4961	ambiguous	0.4124	ambiguous	-0.055	Destabilizing	1.0	D	0.615	neutral	None	None	None	None	N
E/Q	0.2883	likely_benign	0.259	benign	-0.029	Destabilizing	1.0	D	0.681	prob.neutral	N	0.475180673	None	None	N
E/R	0.5682	likely_pathogenic	0.5144	ambiguous	0.264	Stabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	N
E/S	0.4513	ambiguous	0.3866	ambiguous	-0.25	Destabilizing	0.999	D	0.696	prob.neutral	None	None	None	None	N
E/T	0.5202	ambiguous	0.4337	ambiguous	-0.086	Destabilizing	1.0	D	0.641	neutral	None	None	None	None	N
E/V	0.4488	ambiguous	0.3497	ambiguous	-0.055	Destabilizing	1.0	D	0.623	neutral	N	0.505401702	None	None	N
E/W	0.9833	likely_pathogenic	0.9743	pathogenic	-0.331	Destabilizing	1.0	D	0.654	neutral	None	None	None	None	N
E/Y	0.907	likely_pathogenic	0.8719	pathogenic	-0.209	Destabilizing	1.0	D	0.604	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.