TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22667	68224;68225;68226	chr2:178579031;178579030;178579029	chr2:179443758;179443757;179443756
N2AB	21026	63301;63302;63303	chr2:178579031;178579030;178579029	chr2:179443758;179443757;179443756
N2A	20099	60520;60521;60522	chr2:178579031;178579030;178579029	chr2:179443758;179443757;179443756
N2B	13602	41029;41030;41031	chr2:178579031;178579030;178579029	chr2:179443758;179443757;179443756
Novex-1	13727	41404;41405;41406	chr2:178579031;178579030;178579029	chr2:179443758;179443757;179443756
Novex-2	13794	41605;41606;41607	chr2:178579031;178579030;178579029	chr2:179443758;179443757;179443756
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-52
• Domain position: 25
• Structural Position: 26
• Q(SASA): 0.4391
• 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/H	None	None	1.0	N	0.866	0.446	0.554037457546	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
P/A	0.0596	likely_benign	0.0558	benign	-1.554	Destabilizing	0.996	D	0.625	neutral	N	0.48995098	None	None	N
P/C	0.4653	ambiguous	0.4085	ambiguous	-1.074	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
P/D	0.6129	likely_pathogenic	0.5722	pathogenic	-1.562	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
P/E	0.2968	likely_benign	0.2697	benign	-1.501	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
P/F	0.5383	ambiguous	0.4491	ambiguous	-1.114	Destabilizing	1.0	D	0.876	deleterious	None	None	None	None	N
P/G	0.4066	ambiguous	0.3349	benign	-1.915	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
P/H	0.3045	likely_benign	0.2492	benign	-1.386	Destabilizing	1.0	D	0.866	deleterious	N	0.501863892	None	None	N
P/I	0.204	likely_benign	0.1895	benign	-0.634	Destabilizing	0.998	D	0.803	deleterious	None	None	None	None	N
P/K	0.3146	likely_benign	0.2887	benign	-1.381	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
P/L	0.1129	likely_benign	0.0956	benign	-0.634	Destabilizing	0.998	D	0.787	deleterious	N	0.501356913	None	None	N
P/M	0.2483	likely_benign	0.2159	benign	-0.57	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
P/N	0.4522	ambiguous	0.3931	ambiguous	-1.301	Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	N
P/Q	0.18	likely_benign	0.1535	benign	-1.371	Destabilizing	1.0	D	0.876	deleterious	None	None	None	None	N
P/R	0.2518	likely_benign	0.223	benign	-0.929	Destabilizing	1.0	D	0.885	deleterious	N	0.485632514	None	None	N
P/S	0.1384	likely_benign	0.1193	benign	-1.806	Destabilizing	0.999	D	0.817	deleterious	N	0.487354035	None	None	N
P/T	0.1205	likely_benign	0.1078	benign	-1.618	Destabilizing	0.999	D	0.781	deleterious	N	0.487607524	None	None	N
P/V	0.1362	likely_benign	0.1278	benign	-0.908	Destabilizing	0.91	D	0.451	neutral	None	None	None	None	N
P/W	0.7973	likely_pathogenic	0.7197	pathogenic	-1.353	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
P/Y	0.556	ambiguous	0.4668	ambiguous	-1.041	Destabilizing	1.0	D	0.87	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.