TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26864	80815;80816;80817	chr2:178565542;178565541;178565540	chr2:179430269;179430268;179430267
N2AB	25223	75892;75893;75894	chr2:178565542;178565541;178565540	chr2:179430269;179430268;179430267
N2A	24296	73111;73112;73113	chr2:178565542;178565541;178565540	chr2:179430269;179430268;179430267
N2B	17799	53620;53621;53622	chr2:178565542;178565541;178565540	chr2:179430269;179430268;179430267
Novex-1	17924	53995;53996;53997	chr2:178565542;178565541;178565540	chr2:179430269;179430268;179430267
Novex-2	17991	54196;54197;54198	chr2:178565542;178565541;178565540	chr2:179430269;179430268;179430267
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-83
• Domain position: 85
• Structural Position: 120
• Q(SASA): 0.2384
• 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
P/A	rs1296708710	-1.74	1.0	N	0.741	0.424	0.339316883193	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
P/A	rs1296708710	-1.74	1.0	N	0.741	0.424	0.339316883193	gnomAD-4.0.0	1.5917E-06	None	None	None	None	N	None	0	2.28666E-05	None	0	0	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
P/A	0.1343	likely_benign	0.1072	benign	-1.589	Destabilizing	1.0	D	0.741	deleterious	N	0.470479731	None	None	N
P/C	0.6879	likely_pathogenic	0.6224	pathogenic	-0.888	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
P/D	0.8448	likely_pathogenic	0.7701	pathogenic	-1.542	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
P/E	0.743	likely_pathogenic	0.6365	pathogenic	-1.571	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
P/F	0.6684	likely_pathogenic	0.528	ambiguous	-1.29	Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
P/G	0.5237	ambiguous	0.4342	ambiguous	-1.872	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
P/H	0.5414	ambiguous	0.4296	ambiguous	-1.353	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
P/I	0.6805	likely_pathogenic	0.5641	pathogenic	-0.915	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
P/K	0.8994	likely_pathogenic	0.8484	pathogenic	-1.352	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
P/L	0.4733	ambiguous	0.3499	ambiguous	-0.915	Destabilizing	1.0	D	0.835	deleterious	N	0.508320855	None	None	N
P/M	0.6803	likely_pathogenic	0.563	ambiguous	-0.599	Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
P/N	0.8	likely_pathogenic	0.6991	pathogenic	-1.063	Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
P/Q	0.6364	likely_pathogenic	0.5136	ambiguous	-1.304	Destabilizing	1.0	D	0.813	deleterious	D	0.539973916	None	None	N
P/R	0.8102	likely_pathogenic	0.7149	pathogenic	-0.705	Destabilizing	1.0	D	0.864	deleterious	N	0.507373031	None	None	N
P/S	0.253	likely_benign	0.1936	benign	-1.517	Destabilizing	1.0	D	0.775	deleterious	N	0.492218063	None	None	N
P/T	0.3511	ambiguous	0.2622	benign	-1.453	Destabilizing	1.0	D	0.77	deleterious	N	0.516843232	None	None	N
P/V	0.5482	ambiguous	0.436	ambiguous	-1.107	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
P/W	0.8019	likely_pathogenic	0.7319	pathogenic	-1.437	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
P/Y	0.7207	likely_pathogenic	0.6055	pathogenic	-1.198	Destabilizing	1.0	D	0.856	deleterious	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.