TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24216	72871;72872;72873	chr2:178573486;178573485;178573484	chr2:179438213;179438212;179438211
N2AB	22575	67948;67949;67950	chr2:178573486;178573485;178573484	chr2:179438213;179438212;179438211
N2A	21648	65167;65168;65169	chr2:178573486;178573485;178573484	chr2:179438213;179438212;179438211
N2B	15151	45676;45677;45678	chr2:178573486;178573485;178573484	chr2:179438213;179438212;179438211
Novex-1	15276	46051;46052;46053	chr2:178573486;178573485;178573484	chr2:179438213;179438212;179438211
Novex-2	15343	46252;46253;46254	chr2:178573486;178573485;178573484	chr2:179438213;179438212;179438211
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Fn3-63
• Domain position: 95
• Structural Position: 130
• Q(SASA): 0.0855
• 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
A/V	rs1430603849	None	0.78	N	0.543	0.186	0.399740851666	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	4.83E-05	0	0	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
A/C	0.5258	ambiguous	0.5418	ambiguous	-1.744	Destabilizing	0.029	N	0.427	neutral	None	None	None	None	N
A/D	0.9852	likely_pathogenic	0.9908	pathogenic	-2.272	Highly Destabilizing	0.995	D	0.705	prob.delet.	None	None	None	None	N
A/E	0.9716	likely_pathogenic	0.9788	pathogenic	-2.214	Highly Destabilizing	0.981	D	0.677	prob.neutral	N	0.514854995	None	None	N
A/F	0.7888	likely_pathogenic	0.8391	pathogenic	-1.138	Destabilizing	0.971	D	0.685	prob.delet.	None	None	None	None	N
A/G	0.4785	ambiguous	0.5058	ambiguous	-1.481	Destabilizing	0.935	D	0.59	neutral	N	0.496497251	None	None	N
A/H	0.9788	likely_pathogenic	0.9839	pathogenic	-1.5	Destabilizing	0.999	D	0.691	prob.delet.	None	None	None	None	N
A/I	0.516	ambiguous	0.5506	ambiguous	-0.425	Destabilizing	0.943	D	0.711	prob.delet.	None	None	None	None	N
A/K	0.9923	likely_pathogenic	0.9946	pathogenic	-1.332	Destabilizing	0.971	D	0.64	neutral	None	None	None	None	N
A/L	0.3773	ambiguous	0.4203	ambiguous	-0.425	Destabilizing	0.618	D	0.584	neutral	None	None	None	None	N
A/M	0.3534	ambiguous	0.3995	ambiguous	-0.702	Destabilizing	0.66	D	0.512	neutral	None	None	None	None	N
A/N	0.9453	likely_pathogenic	0.9589	pathogenic	-1.431	Destabilizing	0.995	D	0.684	prob.delet.	None	None	None	None	N
A/P	0.7238	likely_pathogenic	0.774	pathogenic	-0.635	Destabilizing	0.994	D	0.681	prob.neutral	N	0.48810346	None	None	N
A/Q	0.9381	likely_pathogenic	0.9505	pathogenic	-1.533	Destabilizing	0.985	D	0.633	neutral	None	None	None	None	N
A/R	0.9777	likely_pathogenic	0.9831	pathogenic	-1.088	Destabilizing	0.985	D	0.676	prob.neutral	None	None	None	None	N
A/S	0.2895	likely_benign	0.3239	benign	-1.814	Destabilizing	0.935	D	0.575	neutral	N	0.502320148	None	None	N
A/T	0.4281	ambiguous	0.5033	ambiguous	-1.657	Destabilizing	0.877	D	0.635	neutral	N	0.504048067	None	None	N
A/V	0.296	likely_benign	0.3245	benign	-0.635	Destabilizing	0.78	D	0.543	neutral	N	0.510336534	None	None	N
A/W	0.9836	likely_pathogenic	0.9886	pathogenic	-1.546	Destabilizing	0.999	D	0.752	deleterious	None	None	None	None	N
A/Y	0.9455	likely_pathogenic	0.9623	pathogenic	-1.109	Destabilizing	0.985	D	0.681	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.