TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24409	73450;73451;73452	chr2:178572907;178572906;178572905	chr2:179437634;179437633;179437632
N2AB	22768	68527;68528;68529	chr2:178572907;178572906;178572905	chr2:179437634;179437633;179437632
N2A	21841	65746;65747;65748	chr2:178572907;178572906;178572905	chr2:179437634;179437633;179437632
N2B	15344	46255;46256;46257	chr2:178572907;178572906;178572905	chr2:179437634;179437633;179437632
Novex-1	15469	46630;46631;46632	chr2:178572907;178572906;178572905	chr2:179437634;179437633;179437632
Novex-2	15536	46831;46832;46833	chr2:178572907;178572906;178572905	chr2:179437634;179437633;179437632
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: Fn3-65
• Domain position: 87
• Structural Position: 119
• Q(SASA): 0.5835
• 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
E/Q	rs762601217	-0.413	1.0	N	0.658	0.323	0.265929055128	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	5.63E-05	None	0	None	0	0	0
E/Q	rs762601217	-0.413	1.0	N	0.658	0.323	0.265929055128	gnomAD-4.0.0	1.59221E-06	None	None	None	None	I	None	0	0	None	0	2.78396E-05	None	0	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	0.3842	ambiguous	0.3532	ambiguous	-0.569	Destabilizing	0.999	D	0.677	prob.neutral	N	0.511958261	None	None	I
E/C	0.9343	likely_pathogenic	0.9265	pathogenic	-0.401	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	I
E/D	0.1316	likely_benign	0.127	benign	-0.501	Destabilizing	0.999	D	0.545	neutral	N	0.504840288	None	None	I
E/F	0.8989	likely_pathogenic	0.8861	pathogenic	-0.153	Destabilizing	1.0	D	0.641	neutral	None	None	None	None	I
E/G	0.441	ambiguous	0.4088	ambiguous	-0.807	Destabilizing	1.0	D	0.666	neutral	N	0.520730799	None	None	I
E/H	0.7644	likely_pathogenic	0.7337	pathogenic	0.194	Stabilizing	1.0	D	0.583	neutral	None	None	None	None	I
E/I	0.5807	likely_pathogenic	0.536	ambiguous	0.044	Stabilizing	1.0	D	0.667	neutral	None	None	None	None	I
E/K	0.3557	ambiguous	0.3146	benign	0.027	Stabilizing	0.999	D	0.641	neutral	D	0.522636615	None	None	I
E/L	0.6353	likely_pathogenic	0.5911	pathogenic	0.044	Stabilizing	1.0	D	0.676	prob.neutral	None	None	None	None	I
E/M	0.675	likely_pathogenic	0.6322	pathogenic	0.048	Stabilizing	1.0	D	0.637	neutral	None	None	None	None	I
E/N	0.4227	ambiguous	0.3939	ambiguous	-0.454	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	I
E/P	0.6722	likely_pathogenic	0.694	pathogenic	-0.141	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	I
E/Q	0.288	likely_benign	0.2542	benign	-0.373	Destabilizing	1.0	D	0.658	neutral	N	0.481332738	None	None	I
E/R	0.5713	likely_pathogenic	0.5274	ambiguous	0.423	Stabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	I
E/S	0.407	ambiguous	0.377	ambiguous	-0.632	Destabilizing	0.999	D	0.683	prob.neutral	None	None	None	None	I
E/T	0.4858	ambiguous	0.4452	ambiguous	-0.425	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	I
E/V	0.418	ambiguous	0.3734	ambiguous	-0.141	Destabilizing	1.0	D	0.699	prob.neutral	N	0.482600186	None	None	I
E/W	0.9722	likely_pathogenic	0.9681	pathogenic	0.103	Stabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	I
E/Y	0.8108	likely_pathogenic	0.7887	pathogenic	0.11	Stabilizing	1.0	D	0.664	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.