TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28319	85180;85181;85182	chr2:178561177;178561176;178561175	chr2:179425904;179425903;179425902
N2AB	26678	80257;80258;80259	chr2:178561177;178561176;178561175	chr2:179425904;179425903;179425902
N2A	25751	77476;77477;77478	chr2:178561177;178561176;178561175	chr2:179425904;179425903;179425902
N2B	19254	57985;57986;57987	chr2:178561177;178561176;178561175	chr2:179425904;179425903;179425902
Novex-1	19379	58360;58361;58362	chr2:178561177;178561176;178561175	chr2:179425904;179425903;179425902
Novex-2	19446	58561;58562;58563	chr2:178561177;178561176;178561175	chr2:179425904;179425903;179425902
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: Fn3-94
• Domain position: 68
• Structural Position: 99
• Q(SASA): 0.4362
• 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/A	rs903892310	-0.684	0.958	N	0.645	0.507	0.393623145366	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
E/A	rs903892310	-0.684	0.958	N	0.645	0.507	0.393623145366	gnomAD-4.0.0	6.36685E-06	None	None	None	None	N	None	0	9.14746E-05	None	0	0	None	0	0	0	0	0
E/D	None	None	0.067	N	0.199	0.166	0.191931220699	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
E/K	None	None	0.958	N	0.635	0.401	0.384919354899	gnomAD-4.0.0	1.59175E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.88865E-05	0	0	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	0.3658	ambiguous	0.3179	benign	-0.742	Destabilizing	0.958	D	0.645	neutral	N	0.468606853	None	None	N
E/C	0.977	likely_pathogenic	0.9746	pathogenic	-0.343	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
E/D	0.6527	likely_pathogenic	0.6494	pathogenic	-0.982	Destabilizing	0.067	N	0.199	neutral	N	0.497666248	None	None	N
E/F	0.9835	likely_pathogenic	0.9799	pathogenic	-0.531	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
E/G	0.5347	ambiguous	0.4904	ambiguous	-1.039	Destabilizing	0.988	D	0.633	neutral	N	0.491830124	None	None	N
E/H	0.9345	likely_pathogenic	0.9168	pathogenic	-0.744	Destabilizing	1.0	D	0.665	neutral	None	None	None	None	N
E/I	0.82	likely_pathogenic	0.7815	pathogenic	0.044	Stabilizing	0.995	D	0.719	prob.delet.	None	None	None	None	N
E/K	0.5085	ambiguous	0.424	ambiguous	-0.433	Destabilizing	0.958	D	0.635	neutral	N	0.488587667	None	None	N
E/L	0.8902	likely_pathogenic	0.8639	pathogenic	0.044	Stabilizing	0.995	D	0.699	prob.neutral	None	None	None	None	N
E/M	0.8441	likely_pathogenic	0.8035	pathogenic	0.407	Stabilizing	1.0	D	0.668	neutral	None	None	None	None	N
E/N	0.8132	likely_pathogenic	0.7904	pathogenic	-0.741	Destabilizing	0.982	D	0.71	prob.delet.	None	None	None	None	N
E/P	0.7532	likely_pathogenic	0.746	pathogenic	-0.197	Destabilizing	0.995	D	0.673	neutral	None	None	None	None	N
E/Q	0.3258	likely_benign	0.2803	benign	-0.683	Destabilizing	0.994	D	0.693	prob.neutral	N	0.477320267	None	None	N
E/R	0.6912	likely_pathogenic	0.6153	pathogenic	-0.222	Destabilizing	0.995	D	0.691	prob.neutral	None	None	None	None	N
E/S	0.6012	likely_pathogenic	0.5592	ambiguous	-1.001	Destabilizing	0.968	D	0.65	neutral	None	None	None	None	N
E/T	0.6707	likely_pathogenic	0.6112	pathogenic	-0.768	Destabilizing	0.991	D	0.685	prob.neutral	None	None	None	None	N
E/V	0.6118	likely_pathogenic	0.5598	ambiguous	-0.197	Destabilizing	0.994	D	0.677	prob.neutral	N	0.484993269	None	None	N
E/W	0.9954	likely_pathogenic	0.9944	pathogenic	-0.37	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
E/Y	0.9751	likely_pathogenic	0.9702	pathogenic	-0.303	Destabilizing	1.0	D	0.683	prob.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.