TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14724	44395;44396;44397	chr2:178630352;178630351;178630350	chr2:179495079;179495078;179495077
N2AB	13083	39472;39473;39474	chr2:178630352;178630351;178630350	chr2:179495079;179495078;179495077
N2A	12156	36691;36692;36693	chr2:178630352;178630351;178630350	chr2:179495079;179495078;179495077
N2B	5659	17200;17201;17202	chr2:178630352;178630351;178630350	chr2:179495079;179495078;179495077
Novex-1	5784	17575;17576;17577	chr2:178630352;178630351;178630350	chr2:179495079;179495078;179495077
Novex-2	5851	17776;17777;17778	chr2:178630352;178630351;178630350	chr2:179495079;179495078;179495077
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-98
• Domain position: 50
• Structural Position: 127
• Q(SASA): 0.4703
• 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	rs1458591077	0.233	0.983	N	0.547	0.266	0.284539287134	gnomAD-2.1.1	8.22E-06	None	None	None	None	N	None	6.49E-05	3E-05	None	0	0	None	0	None	0	0	0
E/K	rs1458591077	0.233	0.983	N	0.547	0.266	0.284539287134	gnomAD-4.0.0	1.60181E-06	None	None	None	None	N	None	0	2.3297E-05	None	0	0	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	0.2328	likely_benign	0.2428	benign	-0.484	Destabilizing	0.991	D	0.579	neutral	N	0.430035451	None	None	N
E/C	0.9249	likely_pathogenic	0.9385	pathogenic	-0.269	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
E/D	0.4544	ambiguous	0.4685	ambiguous	-0.965	Destabilizing	0.991	D	0.532	neutral	N	0.512146346	None	None	N
E/F	0.9229	likely_pathogenic	0.9297	pathogenic	-0.414	Destabilizing	1.0	D	0.725	deleterious	None	None	None	None	N
E/G	0.2591	likely_benign	0.2882	benign	-0.801	Destabilizing	0.999	D	0.677	prob.neutral	N	0.51130285	None	None	N
E/H	0.7733	likely_pathogenic	0.8258	pathogenic	-0.952	Destabilizing	1.0	D	0.649	prob.neutral	None	None	None	None	N
E/I	0.6199	likely_pathogenic	0.5784	pathogenic	0.361	Stabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
E/K	0.2403	likely_benign	0.2841	benign	-0.81	Destabilizing	0.983	D	0.547	neutral	N	0.420039463	None	None	N
E/L	0.7222	likely_pathogenic	0.7186	pathogenic	0.361	Stabilizing	0.999	D	0.724	deleterious	None	None	None	None	N
E/M	0.6607	likely_pathogenic	0.6407	pathogenic	0.778	Stabilizing	1.0	D	0.69	prob.delet.	None	None	None	None	N
E/N	0.5804	likely_pathogenic	0.5989	pathogenic	-0.912	Destabilizing	0.999	D	0.706	prob.delet.	None	None	None	None	N
E/P	0.8722	likely_pathogenic	0.9185	pathogenic	0.101	Stabilizing	1.0	D	0.776	deleterious	None	None	None	None	N
E/Q	0.1912	likely_benign	0.2297	benign	-0.769	Destabilizing	0.911	D	0.259	neutral	N	0.434138767	None	None	N
E/R	0.3944	ambiguous	0.4728	ambiguous	-0.727	Destabilizing	0.998	D	0.709	prob.delet.	None	None	None	None	N
E/S	0.3855	ambiguous	0.4119	ambiguous	-1.203	Destabilizing	0.993	D	0.623	neutral	None	None	None	None	N
E/T	0.3642	ambiguous	0.3472	ambiguous	-0.966	Destabilizing	0.999	D	0.733	deleterious	None	None	None	None	N
E/V	0.3542	ambiguous	0.3151	benign	0.101	Stabilizing	0.999	D	0.727	deleterious	N	0.433454706	None	None	N
E/W	0.9658	likely_pathogenic	0.9753	pathogenic	-0.448	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
E/Y	0.8591	likely_pathogenic	0.8847	pathogenic	-0.283	Destabilizing	1.0	D	0.723	deleterious	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.