TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8791	26596;26597;26598	chr2:178714403;178714402;178714401	chr2:179579130;179579129;179579128
N2AB	8474	25645;25646;25647	chr2:178714403;178714402;178714401	chr2:179579130;179579129;179579128
N2A	7547	22864;22865;22866	chr2:178714403;178714402;178714401	chr2:179579130;179579129;179579128
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: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-73
• Domain position: 56
• Structural Position: 135
• Q(SASA): 0.142
• 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/F	None	None	0.02	N	0.445	0.187	0.331365685468	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	None	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
I/A	0.0969	likely_benign	0.1287	benign	-1.844	Destabilizing	0.006	N	0.335	neutral	None	None	None	None	N
I/C	0.4301	ambiguous	0.5116	ambiguous	-1.307	Destabilizing	0.326	N	0.495	neutral	None	None	None	None	N
I/D	0.2886	likely_benign	0.346	ambiguous	-1.53	Destabilizing	0.014	N	0.5	neutral	None	None	None	None	N
I/E	0.21	likely_benign	0.2327	benign	-1.512	Destabilizing	None	N	0.331	neutral	None	None	None	None	N
I/F	0.0973	likely_benign	0.1275	benign	-1.421	Destabilizing	0.02	N	0.445	neutral	N	0.492342282	None	None	N
I/G	0.2908	likely_benign	0.3753	ambiguous	-2.178	Highly Destabilizing	0.027	N	0.501	neutral	None	None	None	None	N
I/H	0.2005	likely_benign	0.235	benign	-1.399	Destabilizing	0.167	N	0.583	neutral	None	None	None	None	N
I/K	0.1141	likely_benign	0.1298	benign	-1.103	Destabilizing	None	N	0.329	neutral	None	None	None	None	N
I/L	0.0896	likely_benign	0.1103	benign	-0.983	Destabilizing	None	N	0.307	neutral	N	0.479206417	None	None	N
I/M	0.0713	likely_benign	0.0826	benign	-0.825	Destabilizing	0.021	N	0.43	neutral	D	0.532155467	None	None	N
I/N	0.1039	likely_benign	0.1099	benign	-0.979	Destabilizing	None	N	0.343	neutral	N	0.49827218	None	None	N
I/P	0.6631	likely_pathogenic	0.7944	pathogenic	-1.241	Destabilizing	0.121	N	0.587	neutral	None	None	None	None	N
I/Q	0.1642	likely_benign	0.1957	benign	-1.193	Destabilizing	0.001	N	0.36	neutral	None	None	None	None	N
I/R	0.0834	likely_benign	0.0998	benign	-0.55	Destabilizing	0.006	N	0.52	neutral	None	None	None	None	N
I/S	0.0991	likely_benign	0.1116	benign	-1.635	Destabilizing	0.005	N	0.44	neutral	N	0.507353023	None	None	N
I/T	0.0551	likely_benign	0.0656	benign	-1.501	Destabilizing	None	N	0.161	neutral	N	0.440109311	None	None	N
I/V	0.0603	likely_benign	0.0718	benign	-1.241	Destabilizing	None	N	0.095	neutral	N	0.42452657	None	None	N
I/W	0.4889	ambiguous	0.6257	pathogenic	-1.489	Destabilizing	0.892	D	0.577	neutral	None	None	None	None	N
I/Y	0.2662	likely_benign	0.2915	benign	-1.236	Destabilizing	0.006	N	0.564	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.