TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15089	45490;45491;45492	chr2:178621559;178621558;178621557	chr2:179486286;179486285;179486284
N2AB	13448	40567;40568;40569	chr2:178621559;178621558;178621557	chr2:179486286;179486285;179486284
N2A	12521	37786;37787;37788	chr2:178621559;178621558;178621557	chr2:179486286;179486285;179486284
N2B	6024	18295;18296;18297	chr2:178621559;178621558;178621557	chr2:179486286;179486285;179486284
Novex-1	6149	18670;18671;18672	chr2:178621559;178621558;178621557	chr2:179486286;179486285;179486284
Novex-2	6216	18871;18872;18873	chr2:178621559;178621558;178621557	chr2:179486286;179486285;179486284
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-102
• Domain position: 59
• Structural Position: 140
• Q(SASA): 0.0861
• 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/T	None	None	0.989	D	0.757	0.747	0.901871528509	gnomAD-4.0.0	1.59375E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43332E-05	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	0.9617	likely_pathogenic	0.9559	pathogenic	-2.937	Highly Destabilizing	0.992	D	0.688	prob.neutral	None	None	None	None	N
I/C	0.9544	likely_pathogenic	0.9566	pathogenic	-2.192	Highly Destabilizing	1.0	D	0.766	deleterious	None	None	None	None	N
I/D	0.9976	likely_pathogenic	0.9967	pathogenic	-3.6	Highly Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
I/E	0.9934	likely_pathogenic	0.9915	pathogenic	-3.331	Highly Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
I/F	0.4327	ambiguous	0.396	ambiguous	-1.776	Destabilizing	0.998	D	0.721	prob.delet.	D	0.73087708	None	None	N
I/G	0.992	likely_pathogenic	0.9913	pathogenic	-3.522	Highly Destabilizing	1.0	D	0.872	deleterious	None	None	None	None	N
I/H	0.9779	likely_pathogenic	0.9734	pathogenic	-2.993	Highly Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
I/K	0.9799	likely_pathogenic	0.9741	pathogenic	-2.428	Highly Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	N
I/L	0.2762	likely_benign	0.2635	benign	-1.207	Destabilizing	0.889	D	0.387	neutral	D	0.617138406	None	None	N
I/M	0.304	likely_benign	0.2789	benign	-1.143	Destabilizing	0.998	D	0.689	prob.neutral	D	0.758986935	None	None	N
I/N	0.9612	likely_pathogenic	0.9517	pathogenic	-2.938	Highly Destabilizing	0.999	D	0.878	deleterious	D	0.844697701	None	None	N
I/P	0.9973	likely_pathogenic	0.9967	pathogenic	-1.77	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
I/Q	0.9796	likely_pathogenic	0.9744	pathogenic	-2.737	Highly Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
I/R	0.9686	likely_pathogenic	0.9591	pathogenic	-2.135	Highly Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
I/S	0.9562	likely_pathogenic	0.9471	pathogenic	-3.591	Highly Destabilizing	0.998	D	0.849	deleterious	D	0.844697701	None	None	N
I/T	0.9604	likely_pathogenic	0.9496	pathogenic	-3.172	Highly Destabilizing	0.989	D	0.757	deleterious	D	0.844932823	None	None	N
I/V	0.2317	likely_benign	0.2164	benign	-1.77	Destabilizing	0.333	N	0.258	neutral	D	0.648577337	None	None	N
I/W	0.9765	likely_pathogenic	0.9701	pathogenic	-2.246	Highly Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
I/Y	0.9105	likely_pathogenic	0.9029	pathogenic	-1.99	Destabilizing	1.0	D	0.766	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.