TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23693	71302;71303;71304	chr2:178575055;178575054;178575053	chr2:179439782;179439781;179439780
N2AB	22052	66379;66380;66381	chr2:178575055;178575054;178575053	chr2:179439782;179439781;179439780
N2A	21125	63598;63599;63600	chr2:178575055;178575054;178575053	chr2:179439782;179439781;179439780
N2B	14628	44107;44108;44109	chr2:178575055;178575054;178575053	chr2:179439782;179439781;179439780
Novex-1	14753	44482;44483;44484	chr2:178575055;178575054;178575053	chr2:179439782;179439781;179439780
Novex-2	14820	44683;44684;44685	chr2:178575055;178575054;178575053	chr2:179439782;179439781;179439780
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-130
• Domain position: 57
• Structural Position: 140
• Q(SASA): 0.1492
• 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
I/M	None	None	0.998	D	0.691	0.574	0.73377832567	gnomAD-4.0.0	2.05308E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69875E-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	0.9304	likely_pathogenic	0.9589	pathogenic	-2.775	Highly Destabilizing	0.992	D	0.671	neutral	None	None	None	None	N
I/C	0.9265	likely_pathogenic	0.9517	pathogenic	-2.661	Highly Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
I/D	0.9964	likely_pathogenic	0.9976	pathogenic	-3.796	Highly Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
I/E	0.9905	likely_pathogenic	0.9939	pathogenic	-3.624	Highly Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
I/F	0.4784	ambiguous	0.5447	ambiguous	-1.748	Destabilizing	0.998	D	0.728	prob.delet.	D	0.559487793	None	None	N
I/G	0.9891	likely_pathogenic	0.9935	pathogenic	-3.27	Highly Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
I/H	0.9739	likely_pathogenic	0.9838	pathogenic	-2.667	Highly Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
I/K	0.9667	likely_pathogenic	0.9787	pathogenic	-2.405	Highly Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
I/L	0.2205	likely_benign	0.2688	benign	-1.348	Destabilizing	0.889	D	0.42	neutral	D	0.552061683	None	None	N
I/M	0.205	likely_benign	0.2547	benign	-1.45	Destabilizing	0.998	D	0.691	prob.neutral	D	0.57533571	None	None	N
I/N	0.9482	likely_pathogenic	0.9663	pathogenic	-2.803	Highly Destabilizing	0.999	D	0.857	deleterious	D	0.618305813	None	None	N
I/P	0.9965	likely_pathogenic	0.9974	pathogenic	-1.806	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
I/Q	0.9747	likely_pathogenic	0.9838	pathogenic	-2.752	Highly Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
I/R	0.9529	likely_pathogenic	0.9692	pathogenic	-1.92	Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
I/S	0.9411	likely_pathogenic	0.9635	pathogenic	-3.386	Highly Destabilizing	0.998	D	0.834	deleterious	D	0.592767701	None	None	N
I/T	0.9159	likely_pathogenic	0.949	pathogenic	-3.08	Highly Destabilizing	0.989	D	0.749	deleterious	D	0.601882843	None	None	N
I/V	0.1263	likely_benign	0.1457	benign	-1.806	Destabilizing	0.333	N	0.246	neutral	N	0.51026744	None	None	N
I/W	0.9637	likely_pathogenic	0.9722	pathogenic	-2.18	Highly Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
I/Y	0.9022	likely_pathogenic	0.9306	pathogenic	-1.976	Destabilizing	1.0	D	0.739	prob.delet.	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.