TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26054	78385;78386;78387	chr2:178567972;178567971;178567970	chr2:179432699;179432698;179432697
N2AB	24413	73462;73463;73464	chr2:178567972;178567971;178567970	chr2:179432699;179432698;179432697
N2A	23486	70681;70682;70683	chr2:178567972;178567971;178567970	chr2:179432699;179432698;179432697
N2B	16989	51190;51191;51192	chr2:178567972;178567971;178567970	chr2:179432699;179432698;179432697
Novex-1	17114	51565;51566;51567	chr2:178567972;178567971;178567970	chr2:179432699;179432698;179432697
Novex-2	17181	51766;51767;51768	chr2:178567972;178567971;178567970	chr2:179432699;179432698;179432697
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-77
• Domain position: 65
• Structural Position: 96
• Q(SASA): 0.6636
• 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
N/T	None	None	0.98	N	0.439	0.258	0.337621943819	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	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
N/A	0.1385	likely_benign	0.1579	benign	-0.196	Destabilizing	0.97	D	0.443	neutral	None	None	None	None	N
N/C	0.1616	likely_benign	0.1783	benign	0.314	Stabilizing	1.0	D	0.609	neutral	None	None	None	None	N
N/D	0.1126	likely_benign	0.1297	benign	0.118	Stabilizing	0.98	D	0.472	neutral	N	0.448792217	None	None	N
N/E	0.2818	likely_benign	0.3336	benign	0.063	Stabilizing	0.985	D	0.434	neutral	None	None	None	None	N
N/F	0.3296	likely_benign	0.3749	ambiguous	-0.677	Destabilizing	0.999	D	0.577	neutral	None	None	None	None	N
N/G	0.1377	likely_benign	0.1544	benign	-0.325	Destabilizing	0.965	D	0.464	neutral	None	None	None	None	N
N/H	0.093	likely_benign	0.0984	benign	-0.329	Destabilizing	0.998	D	0.471	neutral	N	0.47261346	None	None	N
N/I	0.1792	likely_benign	0.2025	benign	0.049	Stabilizing	0.998	D	0.569	neutral	N	0.480121878	None	None	N
N/K	0.2372	likely_benign	0.2818	benign	0.153	Stabilizing	0.98	D	0.433	neutral	N	0.495124726	None	None	N
N/L	0.1765	likely_benign	0.1855	benign	0.049	Stabilizing	0.996	D	0.498	neutral	None	None	None	None	N
N/M	0.2277	likely_benign	0.2489	benign	0.275	Stabilizing	1.0	D	0.524	neutral	None	None	None	None	N
N/P	0.3927	ambiguous	0.3738	ambiguous	-0.008	Destabilizing	0.041	N	0.287	neutral	None	None	None	None	N
N/Q	0.2212	likely_benign	0.2514	benign	-0.238	Destabilizing	0.999	D	0.449	neutral	None	None	None	None	N
N/R	0.3067	likely_benign	0.3555	ambiguous	0.241	Stabilizing	0.999	D	0.438	neutral	None	None	None	None	N
N/S	0.0841	likely_benign	0.0917	benign	-0.002	Destabilizing	0.98	D	0.493	neutral	N	0.490449625	None	None	N
N/T	0.1052	likely_benign	0.1191	benign	0.068	Stabilizing	0.98	D	0.439	neutral	N	0.479614899	None	None	N
N/V	0.1718	likely_benign	0.1931	benign	-0.008	Destabilizing	0.996	D	0.507	neutral	None	None	None	None	N
N/W	0.6416	likely_pathogenic	0.7032	pathogenic	-0.73	Destabilizing	1.0	D	0.673	neutral	None	None	None	None	N
N/Y	0.1175	likely_benign	0.1293	benign	-0.436	Destabilizing	0.998	D	0.528	neutral	N	0.509328949	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.