TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7247	21964;21965;21966	chr2:178723268;178723267;178723266	chr2:179587995;179587994;179587993
N2AB	6930	21013;21014;21015	chr2:178723268;178723267;178723266	chr2:179587995;179587994;179587993
N2A	6003	18232;18233;18234	chr2:178723268;178723267;178723266	chr2:179587995;179587994;179587993
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: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-57
• Domain position: 18
• Structural Position: 28
• Q(SASA): 0.1424
• 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
I/L	None	None	None	N	0.175	0.079	0.107399877778	gnomAD-4.0.0	6.84337E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99569E-07	0	0
I/T	None	None	0.029	N	0.623	0.223	0.445614145163	gnomAD-4.0.0	4.77582E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.57785E-06	0	0
I/V	None	None	None	N	0.175	0.07	0.178374595973	gnomAD-4.0.0	6.84337E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99569E-07	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
I/A	0.6481	likely_pathogenic	0.6671	pathogenic	-2.907	Highly Destabilizing	None	N	0.421	neutral	None	None	None	None	N
I/C	0.8449	likely_pathogenic	0.8457	pathogenic	-2.348	Highly Destabilizing	0.356	N	0.713	prob.delet.	None	None	None	None	N
I/D	0.9832	likely_pathogenic	0.9835	pathogenic	-3.089	Highly Destabilizing	0.356	N	0.754	deleterious	None	None	None	None	N
I/E	0.9665	likely_pathogenic	0.9654	pathogenic	-2.845	Highly Destabilizing	0.356	N	0.755	deleterious	None	None	None	None	N
I/F	0.28	likely_benign	0.3302	benign	-1.759	Destabilizing	None	N	0.397	neutral	None	None	None	None	N
I/G	0.935	likely_pathogenic	0.9425	pathogenic	-3.495	Highly Destabilizing	0.072	N	0.691	prob.neutral	None	None	None	None	N
I/H	0.9387	likely_pathogenic	0.9379	pathogenic	-2.827	Highly Destabilizing	0.864	D	0.725	prob.delet.	None	None	None	None	N
I/K	0.9347	likely_pathogenic	0.9264	pathogenic	-2.327	Highly Destabilizing	0.106	N	0.752	deleterious	N	0.491864625	None	None	N
I/L	0.1298	likely_benign	0.1339	benign	-1.189	Destabilizing	None	N	0.175	neutral	N	0.416417935	None	None	N
I/M	0.1457	likely_benign	0.1545	benign	-1.183	Destabilizing	0.171	N	0.665	neutral	N	0.48502777	None	None	N
I/N	0.8571	likely_pathogenic	0.8438	pathogenic	-2.682	Highly Destabilizing	0.628	D	0.759	deleterious	None	None	None	None	N
I/P	0.9746	likely_pathogenic	0.9779	pathogenic	-1.744	Destabilizing	0.356	N	0.757	deleterious	None	None	None	None	N
I/Q	0.9314	likely_pathogenic	0.9311	pathogenic	-2.528	Highly Destabilizing	0.628	D	0.758	deleterious	None	None	None	None	N
I/R	0.8871	likely_pathogenic	0.8802	pathogenic	-2.007	Highly Destabilizing	0.295	N	0.756	deleterious	N	0.503220931	None	None	N
I/S	0.8072	likely_pathogenic	0.8004	pathogenic	-3.46	Highly Destabilizing	0.038	N	0.646	neutral	None	None	None	None	N
I/T	0.707	likely_pathogenic	0.6745	pathogenic	-3.051	Highly Destabilizing	0.029	N	0.623	neutral	N	0.468645035	None	None	N
I/V	0.075	likely_benign	0.0807	benign	-1.744	Destabilizing	None	N	0.175	neutral	N	0.431403243	None	None	N
I/W	0.9373	likely_pathogenic	0.9462	pathogenic	-2.087	Highly Destabilizing	0.864	D	0.719	prob.delet.	None	None	None	None	N
I/Y	0.7956	likely_pathogenic	0.8218	pathogenic	-1.865	Destabilizing	0.12	N	0.751	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.