TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18588	55987;55988;55989	chr2:178601142;178601141;178601140	chr2:179465869;179465868;179465867
N2AB	16947	51064;51065;51066	chr2:178601142;178601141;178601140	chr2:179465869;179465868;179465867
N2A	16020	48283;48284;48285	chr2:178601142;178601141;178601140	chr2:179465869;179465868;179465867
N2B	9523	28792;28793;28794	chr2:178601142;178601141;178601140	chr2:179465869;179465868;179465867
Novex-1	9648	29167;29168;29169	chr2:178601142;178601141;178601140	chr2:179465869;179465868;179465867
Novex-2	9715	29368;29369;29370	chr2:178601142;178601141;178601140	chr2:179465869;179465868;179465867
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: Fn3-23
• Domain position: 10
• Structural Position: 12
• Q(SASA): 0.3185
• 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/M	None	None	0.81	N	0.574	0.234	0.265929055128	gnomAD-4.0.0	7.14823E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.22006E-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	0.2816	likely_benign	0.303	benign	-1.976	Destabilizing	0.25	N	0.497	neutral	None	None	None	None	N
I/C	0.8043	likely_pathogenic	0.7947	pathogenic	-1.37	Destabilizing	0.992	D	0.6	neutral	None	None	None	None	N
I/D	0.9042	likely_pathogenic	0.9074	pathogenic	-1.463	Destabilizing	0.972	D	0.691	prob.neutral	None	None	None	None	N
I/E	0.7749	likely_pathogenic	0.7913	pathogenic	-1.264	Destabilizing	0.92	D	0.693	prob.neutral	None	None	None	None	N
I/F	0.2953	likely_benign	0.2383	benign	-1.033	Destabilizing	0.681	D	0.576	neutral	N	0.516035929	None	None	N
I/G	0.7964	likely_pathogenic	0.7982	pathogenic	-2.482	Highly Destabilizing	0.92	D	0.695	prob.neutral	None	None	None	None	N
I/H	0.8116	likely_pathogenic	0.8013	pathogenic	-1.659	Destabilizing	0.992	D	0.679	prob.neutral	None	None	None	None	N
I/K	0.6424	likely_pathogenic	0.6581	pathogenic	-1.398	Destabilizing	0.92	D	0.693	prob.neutral	None	None	None	None	N
I/L	0.1497	likely_benign	0.1417	benign	-0.554	Destabilizing	0.002	N	0.185	neutral	N	0.482616789	None	None	N
I/M	0.1141	likely_benign	0.1099	benign	-0.596	Destabilizing	0.81	D	0.574	neutral	N	0.47760021	None	None	N
I/N	0.6036	likely_pathogenic	0.6135	pathogenic	-1.662	Destabilizing	0.963	D	0.7	prob.neutral	N	0.486096133	None	None	N
I/P	0.6247	likely_pathogenic	0.6346	pathogenic	-1.004	Destabilizing	0.972	D	0.689	prob.neutral	None	None	None	None	N
I/Q	0.7102	likely_pathogenic	0.7227	pathogenic	-1.518	Destabilizing	0.972	D	0.702	prob.neutral	None	None	None	None	N
I/R	0.5756	likely_pathogenic	0.576	pathogenic	-1.168	Destabilizing	0.92	D	0.7	prob.neutral	None	None	None	None	N
I/S	0.4731	ambiguous	0.4932	ambiguous	-2.44	Highly Destabilizing	0.896	D	0.627	neutral	N	0.4756252	None	None	N
I/T	0.1568	likely_benign	0.1629	benign	-2.081	Highly Destabilizing	0.549	D	0.563	neutral	N	0.475878689	None	None	N
I/V	0.0885	likely_benign	0.089	benign	-1.004	Destabilizing	0.001	N	0.161	neutral	N	0.424104416	None	None	N
I/W	0.8535	likely_pathogenic	0.8126	pathogenic	-1.248	Destabilizing	0.992	D	0.719	prob.delet.	None	None	None	None	N
I/Y	0.6789	likely_pathogenic	0.6582	pathogenic	-0.955	Destabilizing	0.92	D	0.616	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.