TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26789	80590;80591;80592	chr2:178565767;178565766;178565765	chr2:179430494;179430493;179430492
N2AB	25148	75667;75668;75669	chr2:178565767;178565766;178565765	chr2:179430494;179430493;179430492
N2A	24221	72886;72887;72888	chr2:178565767;178565766;178565765	chr2:179430494;179430493;179430492
N2B	17724	53395;53396;53397	chr2:178565767;178565766;178565765	chr2:179430494;179430493;179430492
Novex-1	17849	53770;53771;53772	chr2:178565767;178565766;178565765	chr2:179430494;179430493;179430492
Novex-2	17916	53971;53972;53973	chr2:178565767;178565766;178565765	chr2:179430494;179430493;179430492
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Fn3-83
• Domain position: 10
• Structural Position: 12
• Q(SASA): 0.382
• 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
L/F	rs1403788853	None	0.998	N	0.758	0.262	0.606186980318	gnomAD-4.0.0	2.05286E-06	None	None	None	None	I	None	8.96915E-05	0	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
L/A	0.8042	likely_pathogenic	0.7448	pathogenic	-1.745	Destabilizing	0.997	D	0.689	prob.neutral	None	None	None	None	I
L/C	0.8503	likely_pathogenic	0.7972	pathogenic	-1.386	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	I
L/D	0.9956	likely_pathogenic	0.993	pathogenic	-0.653	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	I
L/E	0.9704	likely_pathogenic	0.9514	pathogenic	-0.567	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	I
L/F	0.6066	likely_pathogenic	0.5004	ambiguous	-1.034	Destabilizing	0.998	D	0.758	deleterious	N	0.441884887	None	None	I
L/G	0.9693	likely_pathogenic	0.9579	pathogenic	-2.142	Highly Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	I
L/H	0.9306	likely_pathogenic	0.8917	pathogenic	-1.169	Destabilizing	1.0	D	0.867	deleterious	N	0.521407251	None	None	I
L/I	0.1494	likely_benign	0.1305	benign	-0.694	Destabilizing	0.762	D	0.582	neutral	N	0.415199718	None	None	I
L/K	0.9356	likely_pathogenic	0.9064	pathogenic	-1.15	Destabilizing	0.995	D	0.861	deleterious	None	None	None	None	I
L/M	0.2964	likely_benign	0.2485	benign	-0.738	Destabilizing	0.996	D	0.759	deleterious	None	None	None	None	I
L/N	0.971	likely_pathogenic	0.9566	pathogenic	-1.173	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	I
L/P	0.9022	likely_pathogenic	0.85	pathogenic	-1.015	Destabilizing	1.0	D	0.884	deleterious	N	0.475442888	None	None	I
L/Q	0.8926	likely_pathogenic	0.8292	pathogenic	-1.173	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	I
L/R	0.8985	likely_pathogenic	0.8534	pathogenic	-0.718	Destabilizing	0.999	D	0.885	deleterious	N	0.476537026	None	None	I
L/S	0.9502	likely_pathogenic	0.9178	pathogenic	-1.962	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	I
L/T	0.8417	likely_pathogenic	0.7831	pathogenic	-1.725	Destabilizing	0.997	D	0.799	deleterious	None	None	None	None	I
L/V	0.1223	likely_benign	0.1106	benign	-1.015	Destabilizing	0.102	N	0.342	neutral	N	0.318342388	None	None	I
L/W	0.8708	likely_pathogenic	0.8071	pathogenic	-1.083	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	I
L/Y	0.9073	likely_pathogenic	0.8677	pathogenic	-0.864	Destabilizing	0.997	D	0.874	deleterious	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.