TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30017	90274;90275;90276	chr2:178552851;178552850;178552849	chr2:179417578;179417577;179417576
N2AB	28376	85351;85352;85353	chr2:178552851;178552850;178552849	chr2:179417578;179417577;179417576
N2A	27449	82570;82571;82572	chr2:178552851;178552850;178552849	chr2:179417578;179417577;179417576
N2B	20952	63079;63080;63081	chr2:178552851;178552850;178552849	chr2:179417578;179417577;179417576
Novex-1	21077	63454;63455;63456	chr2:178552851;178552850;178552849	chr2:179417578;179417577;179417576
Novex-2	21144	63655;63656;63657	chr2:178552851;178552850;178552849	chr2:179417578;179417577;179417576
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-106
• Domain position: 85
• Structural Position: 119
• Q(SASA): 0.611
• Predicted PPI site: I

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	rs558277631	-0.397	0.054	N	0.171	0.129	0.0846915920261	gnomAD-2.1.1	1.21E-05	None	None	None	None	I	None	0	0	None	0	1.67579E-04	None	0	None	0	0	0
E/D	rs558277631	-0.397	0.054	N	0.171	0.129	0.0846915920261	gnomAD-3.1.2	2.63E-05	None	None	None	None	I	None	0	0	0	0	7.70119E-04	None	0	0	0	0	0
E/D	rs558277631	-0.397	0.054	N	0.171	0.129	0.0846915920261	1000 genomes	3.99361E-04	None	None	None	None	I	None	0	0	None	None	2E-03	0	None	None	None	0	None
E/D	rs558277631	-0.397	0.054	N	0.171	0.129	0.0846915920261	gnomAD-4.0.0	4.95723E-06	None	None	None	None	I	None	0	0	None	0	1.78412E-04	None	0	0	0	0	0
E/K	rs1559211738	None	0.978	N	0.606	0.32	0.356897458496	gnomAD-2.1.1	3.19E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
E/K	rs1559211738	None	0.978	N	0.606	0.32	0.356897458496	gnomAD-4.0.0	1.5913E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85807E-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
E/A	0.2415	likely_benign	0.194	benign	-0.344	Destabilizing	0.989	D	0.593	neutral	N	0.518422874	None	None	I
E/C	0.8934	likely_pathogenic	0.8581	pathogenic	-0.033	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	I
E/D	0.1467	likely_benign	0.1299	benign	-0.342	Destabilizing	0.054	N	0.171	neutral	N	0.477635044	None	None	I
E/F	0.7924	likely_pathogenic	0.7215	pathogenic	-0.298	Destabilizing	0.999	D	0.743	deleterious	None	None	None	None	I
E/G	0.3305	likely_benign	0.279	benign	-0.524	Destabilizing	0.978	D	0.619	neutral	N	0.504766138	None	None	I
E/H	0.6624	likely_pathogenic	0.5764	pathogenic	-0.004	Destabilizing	0.999	D	0.581	neutral	None	None	None	None	I
E/I	0.3468	ambiguous	0.2868	benign	0.091	Stabilizing	0.999	D	0.729	prob.delet.	None	None	None	None	I
E/K	0.2517	likely_benign	0.2123	benign	0.307	Stabilizing	0.978	D	0.606	neutral	N	0.47902856	None	None	I
E/L	0.3821	ambiguous	0.3127	benign	0.091	Stabilizing	0.998	D	0.691	prob.neutral	None	None	None	None	I
E/M	0.4886	ambiguous	0.4172	ambiguous	0.159	Stabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	I
E/N	0.3557	ambiguous	0.286	benign	0.066	Stabilizing	0.983	D	0.625	neutral	None	None	None	None	I
E/P	0.6826	likely_pathogenic	0.6356	pathogenic	-0.034	Destabilizing	0.999	D	0.644	neutral	None	None	None	None	I
E/Q	0.199	likely_benign	0.1681	benign	0.082	Stabilizing	0.989	D	0.636	neutral	N	0.4838015	None	None	I
E/R	0.4389	ambiguous	0.385	ambiguous	0.522	Stabilizing	0.998	D	0.602	neutral	None	None	None	None	I
E/S	0.3218	likely_benign	0.2593	benign	-0.108	Destabilizing	0.983	D	0.575	neutral	None	None	None	None	I
E/T	0.3506	ambiguous	0.2925	benign	0.037	Stabilizing	0.992	D	0.624	neutral	None	None	None	None	I
E/V	0.2161	likely_benign	0.1797	benign	-0.034	Destabilizing	0.999	D	0.611	neutral	N	0.513806488	None	None	I
E/W	0.9514	likely_pathogenic	0.9285	pathogenic	-0.173	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	I
E/Y	0.7025	likely_pathogenic	0.6231	pathogenic	-0.058	Destabilizing	0.999	D	0.73	prob.delet.	None	None	None	None	I

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.