TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33023	99292;99293;99294	chr2:178538762;178538761;178538760	chr2:179403489;179403488;179403487
N2AB	31382	94369;94370;94371	chr2:178538762;178538761;178538760	chr2:179403489;179403488;179403487
N2A	30455	91588;91589;91590	chr2:178538762;178538761;178538760	chr2:179403489;179403488;179403487
N2B	23958	72097;72098;72099	chr2:178538762;178538761;178538760	chr2:179403489;179403488;179403487
Novex-1	24083	72472;72473;72474	chr2:178538762;178538761;178538760	chr2:179403489;179403488;179403487
Novex-2	24150	72673;72674;72675	chr2:178538762;178538761;178538760	chr2:179403489;179403488;179403487
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: Fn3-129
• Domain position: 26
• Structural Position: 28
• Q(SASA): 1.0689
• 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	rs757929496	0.868	0.999	N	0.727	0.378	0.352262096564	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.87E-06	0
E/K	rs757929496	0.868	0.999	N	0.727	0.378	0.352262096564	gnomAD-4.0.0	1.59144E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85863E-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	0.1962	likely_benign	0.1888	benign	-0.207	Destabilizing	0.999	D	0.667	neutral	N	0.482155429	None	None	N
E/C	0.9143	likely_pathogenic	0.8976	pathogenic	-0.001	Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	N
E/D	0.1542	likely_benign	0.1637	benign	-0.252	Destabilizing	0.999	D	0.571	neutral	N	0.503320135	None	None	N
E/F	0.8341	likely_pathogenic	0.8161	pathogenic	-0.179	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
E/G	0.2617	likely_benign	0.2429	benign	-0.373	Destabilizing	1.0	D	0.641	neutral	N	0.468712666	None	None	N
E/H	0.6457	likely_pathogenic	0.6067	pathogenic	0.135	Stabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	N
E/I	0.4311	ambiguous	0.4044	ambiguous	0.183	Stabilizing	1.0	D	0.728	prob.delet.	None	None	None	None	N
E/K	0.2804	likely_benign	0.2397	benign	0.423	Stabilizing	0.999	D	0.727	prob.delet.	N	0.481461996	None	None	N
E/L	0.4626	ambiguous	0.456	ambiguous	0.183	Stabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
E/M	0.6021	likely_pathogenic	0.5862	pathogenic	0.175	Stabilizing	1.0	D	0.702	prob.neutral	None	None	None	None	N
E/N	0.3718	ambiguous	0.364	ambiguous	0.177	Stabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
E/P	0.6674	likely_pathogenic	0.662	pathogenic	0.072	Stabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	N
E/Q	0.2153	likely_benign	0.1968	benign	0.2	Stabilizing	1.0	D	0.663	neutral	N	0.469927207	None	None	N
E/R	0.438	ambiguous	0.3737	ambiguous	0.596	Stabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
E/S	0.2465	likely_benign	0.238	benign	0.022	Stabilizing	0.999	D	0.705	prob.neutral	None	None	None	None	N
E/T	0.2953	likely_benign	0.2786	benign	0.158	Stabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	N
E/V	0.2765	likely_benign	0.259	benign	0.072	Stabilizing	1.0	D	0.712	prob.delet.	N	0.506880515	None	None	N
E/W	0.9526	likely_pathogenic	0.9404	pathogenic	-0.079	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
E/Y	0.7661	likely_pathogenic	0.7415	pathogenic	0.057	Stabilizing	1.0	D	0.701	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.