TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23639	71140;71141;71142	chr2:178575217;178575216;178575215	chr2:179439944;179439943;179439942
N2AB	21998	66217;66218;66219	chr2:178575217;178575216;178575215	chr2:179439944;179439943;179439942
N2A	21071	63436;63437;63438	chr2:178575217;178575216;178575215	chr2:179439944;179439943;179439942
N2B	14574	43945;43946;43947	chr2:178575217;178575216;178575215	chr2:179439944;179439943;179439942
Novex-1	14699	44320;44321;44322	chr2:178575217;178575216;178575215	chr2:179439944;179439943;179439942
Novex-2	14766	44521;44522;44523	chr2:178575217;178575216;178575215	chr2:179439944;179439943;179439942
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Ig-130
• Domain position: 3
• Structural Position: 3
• Q(SASA): 0.172
• 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
Y/H	None	None	0.998	N	0.722	0.362	0.450343601259	gnomAD-4.0.0	6.846E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99701E-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
Y/A	0.6369	likely_pathogenic	0.6297	pathogenic	-0.386	Destabilizing	0.968	D	0.665	neutral	None	None	None	None	N
Y/C	0.2335	likely_benign	0.2129	benign	0.002	Stabilizing	0.999	D	0.763	deleterious	N	0.464636822	None	None	N
Y/D	0.6738	likely_pathogenic	0.6694	pathogenic	0.731	Stabilizing	0.998	D	0.775	deleterious	N	0.511811906	None	None	N
Y/E	0.8719	likely_pathogenic	0.8768	pathogenic	0.7	Stabilizing	0.998	D	0.741	deleterious	None	None	None	None	N
Y/F	0.1383	likely_benign	0.1557	benign	-0.287	Destabilizing	0.067	N	0.351	neutral	N	0.406665954	None	None	N
Y/G	0.5766	likely_pathogenic	0.5479	ambiguous	-0.518	Destabilizing	0.995	D	0.759	deleterious	None	None	None	None	N
Y/H	0.3302	likely_benign	0.343	ambiguous	0.315	Stabilizing	0.998	D	0.722	prob.delet.	N	0.494266296	None	None	N
Y/I	0.7066	likely_pathogenic	0.7134	pathogenic	-0.081	Destabilizing	0.982	D	0.722	prob.delet.	None	None	None	None	N
Y/K	0.8248	likely_pathogenic	0.8187	pathogenic	0.171	Stabilizing	0.995	D	0.737	prob.delet.	None	None	None	None	N
Y/L	0.603	likely_pathogenic	0.6015	pathogenic	-0.081	Destabilizing	0.938	D	0.56	neutral	None	None	None	None	N
Y/M	0.7645	likely_pathogenic	0.7626	pathogenic	-0.168	Destabilizing	0.999	D	0.764	deleterious	None	None	None	None	N
Y/N	0.3987	ambiguous	0.4078	ambiguous	-0.122	Destabilizing	0.998	D	0.757	deleterious	N	0.512331981	None	None	N
Y/P	0.5378	ambiguous	0.5391	ambiguous	-0.165	Destabilizing	0.998	D	0.783	deleterious	None	None	None	None	N
Y/Q	0.6824	likely_pathogenic	0.7041	pathogenic	-0.029	Destabilizing	0.998	D	0.769	deleterious	None	None	None	None	N
Y/R	0.6441	likely_pathogenic	0.6483	pathogenic	0.3	Stabilizing	0.998	D	0.763	deleterious	None	None	None	None	N
Y/S	0.2923	likely_benign	0.2944	benign	-0.425	Destabilizing	0.994	D	0.74	deleterious	N	0.511638548	None	None	N
Y/T	0.5853	likely_pathogenic	0.5835	pathogenic	-0.373	Destabilizing	0.995	D	0.745	deleterious	None	None	None	None	N
Y/V	0.5771	likely_pathogenic	0.5714	pathogenic	-0.165	Destabilizing	0.968	D	0.676	prob.neutral	None	None	None	None	N
Y/W	0.5188	ambiguous	0.5433	ambiguous	-0.538	Destabilizing	1.0	D	0.715	prob.delet.	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.