TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30124	90595;90596;90597	chr2:178552530;178552529;178552528	chr2:179417257;179417256;179417255
N2AB	28483	85672;85673;85674	chr2:178552530;178552529;178552528	chr2:179417257;179417256;179417255
N2A	27556	82891;82892;82893	chr2:178552530;178552529;178552528	chr2:179417257;179417256;179417255
N2B	21059	63400;63401;63402	chr2:178552530;178552529;178552528	chr2:179417257;179417256;179417255
Novex-1	21184	63775;63776;63777	chr2:178552530;178552529;178552528	chr2:179417257;179417256;179417255
Novex-2	21251	63976;63977;63978	chr2:178552530;178552529;178552528	chr2:179417257;179417256;179417255
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: Fn3-107
• Domain position: 95
• Structural Position: 132
• Q(SASA): 0.6679
• 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/V	None	None	0.966	N	0.577	0.354	0.496036935653	gnomAD-4.0.0	1.5914E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85827E-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	0.5256	ambiguous	0.4864	ambiguous	-0.35	Destabilizing	0.799	D	0.61	neutral	N	0.467124475	None	None	N
E/C	0.9804	likely_pathogenic	0.9779	pathogenic	-0.106	Destabilizing	0.998	D	0.834	deleterious	None	None	None	None	N
E/D	0.1269	likely_benign	0.1123	benign	-0.26	Destabilizing	0.002	N	0.208	neutral	N	0.385047383	None	None	N
E/F	0.9847	likely_pathogenic	0.9787	pathogenic	-0.217	Destabilizing	0.991	D	0.674	prob.neutral	None	None	None	None	N
E/G	0.5567	ambiguous	0.4936	ambiguous	-0.527	Destabilizing	0.799	D	0.535	neutral	N	0.468260777	None	None	N
E/H	0.909	likely_pathogenic	0.884	pathogenic	0.111	Stabilizing	0.991	D	0.513	neutral	None	None	None	None	N
E/I	0.9212	likely_pathogenic	0.9141	pathogenic	0.078	Stabilizing	0.974	D	0.712	prob.delet.	None	None	None	None	N
E/K	0.7718	likely_pathogenic	0.7159	pathogenic	0.35	Stabilizing	0.799	D	0.558	neutral	N	0.468007288	None	None	N
E/L	0.911	likely_pathogenic	0.8909	pathogenic	0.078	Stabilizing	0.974	D	0.695	prob.delet.	None	None	None	None	N
E/M	0.9144	likely_pathogenic	0.9	pathogenic	0.104	Stabilizing	0.998	D	0.681	prob.neutral	None	None	None	None	N
E/N	0.5142	ambiguous	0.4742	ambiguous	0.013	Stabilizing	0.725	D	0.625	neutral	None	None	None	None	N
E/P	0.8132	likely_pathogenic	0.7652	pathogenic	-0.045	Destabilizing	0.974	D	0.637	neutral	None	None	None	None	N
E/Q	0.5384	ambiguous	0.4863	ambiguous	0.053	Stabilizing	0.89	D	0.544	neutral	N	0.515859784	None	None	N
E/R	0.8814	likely_pathogenic	0.8432	pathogenic	0.563	Stabilizing	0.974	D	0.617	neutral	None	None	None	None	N
E/S	0.5805	likely_pathogenic	0.5362	ambiguous	-0.139	Destabilizing	0.841	D	0.579	neutral	None	None	None	None	N
E/T	0.7098	likely_pathogenic	0.6947	pathogenic	0.012	Stabilizing	0.841	D	0.639	neutral	None	None	None	None	N
E/V	0.7848	likely_pathogenic	0.7707	pathogenic	-0.045	Destabilizing	0.966	D	0.577	neutral	N	0.46699333	None	None	N
E/W	0.9924	likely_pathogenic	0.9894	pathogenic	-0.065	Destabilizing	0.998	D	0.857	deleterious	None	None	None	None	N
E/Y	0.9437	likely_pathogenic	0.9221	pathogenic	0.025	Stabilizing	0.991	D	0.645	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.