TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9004	27235;27236;27237	chr2:178713124;178713123;178713122	chr2:179577851;179577850;179577849
N2AB	8687	26284;26285;26286	chr2:178713124;178713123;178713122	chr2:179577851;179577850;179577849
N2A	7760	23503;23504;23505	chr2:178713124;178713123;178713122	chr2:179577851;179577850;179577849
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-75
• Domain position: 79
• Structural Position: 163
• Q(SASA): 0.6487
• 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
A/T	None	None	0.892	N	0.517	0.341	0.326881540566	gnomAD-4.0.0	2.05278E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.69853E-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
A/C	0.7414	likely_pathogenic	0.7194	pathogenic	-0.803	Destabilizing	0.999	D	0.581	neutral	None	None	None	None	I
A/D	0.6228	likely_pathogenic	0.6843	pathogenic	-0.646	Destabilizing	0.994	D	0.649	neutral	N	0.511905022	None	None	I
A/E	0.5515	ambiguous	0.6251	pathogenic	-0.803	Destabilizing	0.987	D	0.574	neutral	None	None	None	None	I
A/F	0.4108	ambiguous	0.4623	ambiguous	-0.949	Destabilizing	0.975	D	0.648	neutral	None	None	None	None	I
A/G	0.2964	likely_benign	0.3013	benign	-0.234	Destabilizing	0.944	D	0.525	neutral	N	0.491772851	None	None	I
A/H	0.685	likely_pathogenic	0.7123	pathogenic	-0.213	Destabilizing	0.999	D	0.675	prob.neutral	None	None	None	None	I
A/I	0.4888	ambiguous	0.5527	ambiguous	-0.424	Destabilizing	0.253	N	0.436	neutral	None	None	None	None	I
A/K	0.8213	likely_pathogenic	0.8622	pathogenic	-0.57	Destabilizing	0.987	D	0.569	neutral	None	None	None	None	I
A/L	0.3534	ambiguous	0.4157	ambiguous	-0.424	Destabilizing	0.033	N	0.449	neutral	None	None	None	None	I
A/M	0.4172	ambiguous	0.4626	ambiguous	-0.546	Destabilizing	0.975	D	0.585	neutral	None	None	None	None	I
A/N	0.606	likely_pathogenic	0.6384	pathogenic	-0.25	Destabilizing	0.996	D	0.653	neutral	None	None	None	None	I
A/P	0.9114	likely_pathogenic	0.9278	pathogenic	-0.335	Destabilizing	0.994	D	0.575	neutral	D	0.538403068	None	None	I
A/Q	0.6508	likely_pathogenic	0.6888	pathogenic	-0.539	Destabilizing	0.996	D	0.583	neutral	None	None	None	None	I
A/R	0.6963	likely_pathogenic	0.7432	pathogenic	-0.097	Destabilizing	0.987	D	0.574	neutral	None	None	None	None	I
A/S	0.1714	likely_benign	0.1691	benign	-0.411	Destabilizing	0.944	D	0.546	neutral	N	0.487315852	None	None	I
A/T	0.2682	likely_benign	0.2739	benign	-0.499	Destabilizing	0.892	D	0.517	neutral	N	0.505647144	None	None	I
A/V	0.2047	likely_benign	0.2301	benign	-0.335	Destabilizing	0.63	D	0.505	neutral	N	0.503120639	None	None	I
A/W	0.8328	likely_pathogenic	0.867	pathogenic	-1.045	Destabilizing	0.999	D	0.717	prob.delet.	None	None	None	None	I
A/Y	0.625	likely_pathogenic	0.6652	pathogenic	-0.728	Destabilizing	0.987	D	0.649	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.