TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22419	67480;67481;67482	chr2:178580032;178580031;178580030	chr2:179444759;179444758;179444757
N2AB	20778	62557;62558;62559	chr2:178580032;178580031;178580030	chr2:179444759;179444758;179444757
N2A	19851	59776;59777;59778	chr2:178580032;178580031;178580030	chr2:179444759;179444758;179444757
N2B	13354	40285;40286;40287	chr2:178580032;178580031;178580030	chr2:179444759;179444758;179444757
Novex-1	13479	40660;40661;40662	chr2:178580032;178580031;178580030	chr2:179444759;179444758;179444757
Novex-2	13546	40861;40862;40863	chr2:178580032;178580031;178580030	chr2:179444759;179444758;179444757
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-50
• Domain position: 66
• Structural Position: 98
• Q(SASA): 0.5987
• 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
E/D	None	None	0.722	N	0.455	0.124	0.132336055621	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31252E-06	0	0
E/Q	rs1460379508	-0.314	0.949	N	0.526	0.248	0.231231049324	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
E/Q	rs1460379508	-0.314	0.949	N	0.526	0.248	0.231231049324	gnomAD-4.0.0	1.59227E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02627E-05

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
E/A	0.2453	likely_benign	0.2121	benign	-0.51	Destabilizing	0.565	D	0.536	neutral	N	0.478789837	None	None	N
E/C	0.89	likely_pathogenic	0.8445	pathogenic	-0.329	Destabilizing	0.996	D	0.685	prob.neutral	None	None	None	None	N
E/D	0.2463	likely_benign	0.1932	benign	-0.639	Destabilizing	0.722	D	0.455	neutral	N	0.505264362	None	None	N
E/F	0.8911	likely_pathogenic	0.8491	pathogenic	0.066	Stabilizing	0.961	D	0.645	neutral	None	None	None	None	N
E/G	0.3207	likely_benign	0.2712	benign	-0.8	Destabilizing	0.008	N	0.277	neutral	N	0.506833734	None	None	N
E/H	0.6993	likely_pathogenic	0.5935	pathogenic	0.291	Stabilizing	0.996	D	0.534	neutral	None	None	None	None	N
E/I	0.4531	ambiguous	0.366	ambiguous	0.257	Stabilizing	0.923	D	0.651	neutral	None	None	None	None	N
E/K	0.3453	ambiguous	0.2737	benign	0.075	Stabilizing	0.722	D	0.503	neutral	N	0.451293804	None	None	N
E/L	0.4781	ambiguous	0.3917	ambiguous	0.257	Stabilizing	0.858	D	0.544	neutral	None	None	None	None	N
E/M	0.5927	likely_pathogenic	0.518	ambiguous	0.323	Stabilizing	0.996	D	0.625	neutral	None	None	None	None	N
E/N	0.5041	ambiguous	0.4209	ambiguous	-0.557	Destabilizing	0.923	D	0.499	neutral	None	None	None	None	N
E/P	0.7898	likely_pathogenic	0.7403	pathogenic	0.022	Stabilizing	0.961	D	0.595	neutral	None	None	None	None	N
E/Q	0.208	likely_benign	0.172	benign	-0.441	Destabilizing	0.949	D	0.526	neutral	N	0.430419887	None	None	N
E/R	0.4632	ambiguous	0.3798	ambiguous	0.468	Stabilizing	0.923	D	0.53	neutral	None	None	None	None	N
E/S	0.3664	ambiguous	0.2987	benign	-0.735	Destabilizing	0.633	D	0.481	neutral	None	None	None	None	N
E/T	0.3235	likely_benign	0.2656	benign	-0.48	Destabilizing	0.011	N	0.321	neutral	None	None	None	None	N
E/V	0.2589	likely_benign	0.2082	benign	0.022	Stabilizing	0.82	D	0.487	neutral	N	0.439636803	None	None	N
E/W	0.9553	likely_pathogenic	0.9366	pathogenic	0.353	Stabilizing	0.996	D	0.703	prob.neutral	None	None	None	None	N
E/Y	0.8177	likely_pathogenic	0.7563	pathogenic	0.348	Stabilizing	0.987	D	0.627	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.