TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16885	50878;50879;50880	chr2:178611576;178611575;178611574	chr2:179476303;179476302;179476301
N2AB	15244	45955;45956;45957	chr2:178611576;178611575;178611574	chr2:179476303;179476302;179476301
N2A	14317	43174;43175;43176	chr2:178611576;178611575;178611574	chr2:179476303;179476302;179476301
N2B	7820	23683;23684;23685	chr2:178611576;178611575;178611574	chr2:179476303;179476302;179476301
Novex-1	7945	24058;24059;24060	chr2:178611576;178611575;178611574	chr2:179476303;179476302;179476301
Novex-2	8012	24259;24260;24261	chr2:178611576;178611575;178611574	chr2:179476303;179476302;179476301
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Fn3-11
• Domain position: 34
• Structural Position: 36
• Q(SASA): 0.5003
• 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/T	rs2056332746	None	0.27	N	0.313	0.227	0.469248961376	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.625E-06	0	0
I/V	rs1405647586	-0.494	0.139	N	0.16	0.045	0.382761230579	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.93E-06	0
I/V	rs1405647586	-0.494	0.139	N	0.16	0.045	0.382761230579	gnomAD-4.0.0	5.47609E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	7.19819E-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	0.2553	likely_benign	0.2995	benign	-1.11	Destabilizing	0.013	N	0.135	neutral	None	None	None	None	I
I/C	0.7728	likely_pathogenic	0.7861	pathogenic	-0.671	Destabilizing	0.981	D	0.291	neutral	None	None	None	None	I
I/D	0.8408	likely_pathogenic	0.8859	pathogenic	-0.663	Destabilizing	0.704	D	0.392	neutral	None	None	None	None	I
I/E	0.6777	likely_pathogenic	0.7594	pathogenic	-0.725	Destabilizing	0.704	D	0.357	neutral	None	None	None	None	I
I/F	0.2549	likely_benign	0.2474	benign	-0.892	Destabilizing	0.893	D	0.315	neutral	None	None	None	None	I
I/G	0.6999	likely_pathogenic	0.7489	pathogenic	-1.349	Destabilizing	0.003	N	0.205	neutral	None	None	None	None	I
I/H	0.622	likely_pathogenic	0.6635	pathogenic	-0.638	Destabilizing	0.981	D	0.274	neutral	None	None	None	None	I
I/K	0.5138	ambiguous	0.5949	pathogenic	-0.768	Destabilizing	0.473	N	0.345	neutral	N	0.463108553	None	None	I
I/L	0.0979	likely_benign	0.1019	benign	-0.571	Destabilizing	0.002	N	0.065	neutral	N	0.455996319	None	None	I
I/M	0.1045	likely_benign	0.1104	benign	-0.431	Destabilizing	0.863	D	0.303	neutral	N	0.478242839	None	None	I
I/N	0.3976	ambiguous	0.4765	ambiguous	-0.496	Destabilizing	0.704	D	0.392	neutral	None	None	None	None	I
I/P	0.9334	likely_pathogenic	0.9245	pathogenic	-0.717	Destabilizing	0.944	D	0.382	neutral	None	None	None	None	I
I/Q	0.4929	ambiguous	0.5749	pathogenic	-0.73	Destabilizing	0.893	D	0.369	neutral	None	None	None	None	I
I/R	0.428	ambiguous	0.4911	ambiguous	-0.15	Destabilizing	0.006	N	0.222	neutral	N	0.479142757	None	None	I
I/S	0.2823	likely_benign	0.3337	benign	-0.989	Destabilizing	0.085	N	0.209	neutral	None	None	None	None	I
I/T	0.1085	likely_benign	0.116	benign	-0.942	Destabilizing	0.27	N	0.313	neutral	N	0.407226416	None	None	I
I/V	0.0888	likely_benign	0.0924	benign	-0.717	Destabilizing	0.139	N	0.16	neutral	N	0.473559509	None	None	I
I/W	0.8354	likely_pathogenic	0.8283	pathogenic	-0.926	Destabilizing	0.995	D	0.297	neutral	None	None	None	None	I
I/Y	0.6696	likely_pathogenic	0.6785	pathogenic	-0.707	Destabilizing	0.981	D	0.344	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.