TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29536	88831;88832;88833	chr2:178554741;178554740;178554739	chr2:179419468;179419467;179419466
N2AB	27895	83908;83909;83910	chr2:178554741;178554740;178554739	chr2:179419468;179419467;179419466
N2A	26968	81127;81128;81129	chr2:178554741;178554740;178554739	chr2:179419468;179419467;179419466
N2B	20471	61636;61637;61638	chr2:178554741;178554740;178554739	chr2:179419468;179419467;179419466
Novex-1	20596	62011;62012;62013	chr2:178554741;178554740;178554739	chr2:179419468;179419467;179419466
Novex-2	20663	62212;62213;62214	chr2:178554741;178554740;178554739	chr2:179419468;179419467;179419466
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: Fn3-103
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.2733
• 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/L	rs928055260	None	1.0	N	0.873	0.469	0.721917965023	gnomAD-4.0.0	1.59177E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02535E-05

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	0.0913	likely_benign	0.092	benign	-1.548	Destabilizing	1.0	D	0.819	deleterious	N	0.49967961	None	None	N
P/C	0.4162	ambiguous	0.441	ambiguous	-1.023	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
P/D	0.6747	likely_pathogenic	0.704	pathogenic	-1.603	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
P/E	0.3582	ambiguous	0.3805	ambiguous	-1.634	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
P/F	0.4319	ambiguous	0.4597	ambiguous	-1.33	Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	N
P/G	0.4606	ambiguous	0.4909	ambiguous	-1.831	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
P/H	0.2237	likely_benign	0.2485	benign	-1.341	Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
P/I	0.2285	likely_benign	0.2081	benign	-0.874	Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	N
P/K	0.2145	likely_benign	0.2167	benign	-1.216	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
P/L	0.1166	likely_benign	0.116	benign	-0.874	Destabilizing	1.0	D	0.873	deleterious	N	0.504107801	None	None	N
P/M	0.2634	likely_benign	0.2722	benign	-0.629	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
P/N	0.4798	ambiguous	0.5013	ambiguous	-0.974	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
P/Q	0.1603	likely_benign	0.1686	benign	-1.229	Destabilizing	1.0	D	0.863	deleterious	N	0.492586912	None	None	N
P/R	0.1545	likely_benign	0.1599	benign	-0.631	Destabilizing	1.0	D	0.883	deleterious	N	0.500348819	None	None	N
P/S	0.1813	likely_benign	0.1946	benign	-1.443	Destabilizing	1.0	D	0.844	deleterious	N	0.487978556	None	None	N
P/T	0.1536	likely_benign	0.1491	benign	-1.377	Destabilizing	1.0	D	0.846	deleterious	N	0.490625129	None	None	N
P/V	0.1777	likely_benign	0.1634	benign	-1.065	Destabilizing	1.0	D	0.876	deleterious	None	None	None	None	N
P/W	0.6958	likely_pathogenic	0.7336	pathogenic	-1.47	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
P/Y	0.4644	ambiguous	0.5005	ambiguous	-1.2	Destabilizing	1.0	D	0.885	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.