TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9114	27565;27566;27567	chr2:178712582;178712581;178712580	chr2:179577309;179577308;179577307
N2AB	8797	26614;26615;26616	chr2:178712582;178712581;178712580	chr2:179577309;179577308;179577307
N2A	7870	23833;23834;23835	chr2:178712582;178712581;178712580	chr2:179577309;179577308;179577307
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Ig-77
• Domain position: 3
• Structural Position: 3
• Q(SASA): 0.6685
• 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
F/L	None	None	0.999	D	0.563	0.75	0.604764006798	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
F/A	0.9763	likely_pathogenic	0.9713	pathogenic	-3.282	Highly Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
F/C	0.9472	likely_pathogenic	0.946	pathogenic	-2.234	Highly Destabilizing	1.0	D	0.759	deleterious	D	0.565428681	None	None	N
F/D	0.9966	likely_pathogenic	0.9961	pathogenic	-3.273	Highly Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
F/E	0.9971	likely_pathogenic	0.9969	pathogenic	-3.131	Highly Destabilizing	1.0	D	0.712	prob.delet.	None	None	None	None	N
F/G	0.9916	likely_pathogenic	0.9904	pathogenic	-3.638	Highly Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
F/H	0.982	likely_pathogenic	0.9818	pathogenic	-1.89	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
F/I	0.7125	likely_pathogenic	0.6836	pathogenic	-2.124	Highly Destabilizing	1.0	D	0.669	neutral	N	0.500851431	None	None	N
F/K	0.9977	likely_pathogenic	0.9977	pathogenic	-2.056	Highly Destabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	N
F/L	0.9732	likely_pathogenic	0.9697	pathogenic	-2.124	Highly Destabilizing	0.999	D	0.563	neutral	D	0.525417829	None	None	N
F/M	0.8829	likely_pathogenic	0.8721	pathogenic	-1.975	Destabilizing	1.0	D	0.661	neutral	None	None	None	None	N
F/N	0.9861	likely_pathogenic	0.9851	pathogenic	-2.3	Highly Destabilizing	1.0	D	0.728	prob.delet.	None	None	None	None	N
F/P	0.9983	likely_pathogenic	0.9978	pathogenic	-2.518	Highly Destabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	N
F/Q	0.9955	likely_pathogenic	0.9952	pathogenic	-2.443	Highly Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
F/R	0.9936	likely_pathogenic	0.9933	pathogenic	-1.305	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
F/S	0.9795	likely_pathogenic	0.9774	pathogenic	-2.992	Highly Destabilizing	1.0	D	0.717	prob.delet.	D	0.564921702	None	None	N
F/T	0.979	likely_pathogenic	0.9754	pathogenic	-2.755	Highly Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
F/V	0.7982	likely_pathogenic	0.7855	pathogenic	-2.518	Highly Destabilizing	1.0	D	0.71	prob.delet.	D	0.52465736	None	None	N
F/W	0.8429	likely_pathogenic	0.8127	pathogenic	-0.802	Destabilizing	1.0	D	0.684	prob.neutral	None	None	None	None	N
F/Y	0.4993	ambiguous	0.4856	ambiguous	-1.191	Destabilizing	0.999	D	0.609	neutral	D	0.553818887	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.