TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32657	98194;98195;98196	chr2:178540197;178540196;178540195	chr2:179404924;179404923;179404922
N2AB	31016	93271;93272;93273	chr2:178540197;178540196;178540195	chr2:179404924;179404923;179404922
N2A	30089	90490;90491;90492	chr2:178540197;178540196;178540195	chr2:179404924;179404923;179404922
N2B	23592	70999;71000;71001	chr2:178540197;178540196;178540195	chr2:179404924;179404923;179404922
Novex-1	23717	71374;71375;71376	chr2:178540197;178540196;178540195	chr2:179404924;179404923;179404922
Novex-2	23784	71575;71576;71577	chr2:178540197;178540196;178540195	chr2:179404924;179404923;179404922
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-126
• Domain position: 58
• Structural Position: 88
• Q(SASA): 0.5133
• 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
I/M	rs761994900	None	0.817	N	0.315	0.094	0.355034743287	gnomAD-4.0.0	2.73675E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.59786E-06	0	0
I/N	None	None	0.999	N	0.679	0.44	0.81315104837	gnomAD-4.0.0	1.59115E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85822E-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
I/A	0.7304	likely_pathogenic	0.66	pathogenic	-1.077	Destabilizing	0.985	D	0.52	neutral	None	None	None	None	I
I/C	0.8348	likely_pathogenic	0.7944	pathogenic	-0.844	Destabilizing	1.0	D	0.622	neutral	None	None	None	None	I
I/D	0.8959	likely_pathogenic	0.8575	pathogenic	-0.556	Destabilizing	0.999	D	0.673	neutral	None	None	None	None	I
I/E	0.7863	likely_pathogenic	0.6978	pathogenic	-0.551	Destabilizing	0.999	D	0.674	neutral	None	None	None	None	I
I/F	0.3072	likely_benign	0.298	benign	-0.664	Destabilizing	0.994	D	0.499	neutral	N	0.508109879	None	None	I
I/G	0.8616	likely_pathogenic	0.8067	pathogenic	-1.341	Destabilizing	0.998	D	0.665	neutral	None	None	None	None	I
I/H	0.7913	likely_pathogenic	0.733	pathogenic	-0.334	Destabilizing	1.0	D	0.68	prob.neutral	None	None	None	None	I
I/K	0.7595	likely_pathogenic	0.6806	pathogenic	-0.703	Destabilizing	0.998	D	0.664	neutral	None	None	None	None	I
I/L	0.1858	likely_benign	0.1717	benign	-0.44	Destabilizing	0.061	N	0.133	neutral	N	0.447157421	None	None	I
I/M	0.1361	likely_benign	0.1276	benign	-0.625	Destabilizing	0.817	D	0.315	neutral	N	0.48729189	None	None	I
I/N	0.5046	ambiguous	0.4262	ambiguous	-0.693	Destabilizing	0.999	D	0.679	prob.neutral	N	0.468762057	None	None	I
I/P	0.9413	likely_pathogenic	0.9353	pathogenic	-0.622	Destabilizing	0.999	D	0.677	prob.neutral	None	None	None	None	I
I/Q	0.6804	likely_pathogenic	0.5889	pathogenic	-0.8	Destabilizing	0.998	D	0.68	prob.neutral	None	None	None	None	I
I/R	0.7142	likely_pathogenic	0.6442	pathogenic	-0.172	Destabilizing	0.998	D	0.67	neutral	None	None	None	None	I
I/S	0.6271	likely_pathogenic	0.5374	ambiguous	-1.221	Destabilizing	0.997	D	0.545	neutral	N	0.448464143	None	None	I
I/T	0.6574	likely_pathogenic	0.5883	pathogenic	-1.093	Destabilizing	0.99	D	0.512	neutral	N	0.43972723	None	None	I
I/V	0.1776	likely_benign	0.1731	benign	-0.622	Destabilizing	0.817	D	0.298	neutral	N	0.420221536	None	None	I
I/W	0.8498	likely_pathogenic	0.8353	pathogenic	-0.708	Destabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	I
I/Y	0.6473	likely_pathogenic	0.5754	pathogenic	-0.48	Destabilizing	0.999	D	0.616	neutral	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.