TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20182	60769;60770;60771	chr2:178591181;178591180;178591179	chr2:179455908;179455907;179455906
N2AB	18541	55846;55847;55848	chr2:178591181;178591180;178591179	chr2:179455908;179455907;179455906
N2A	17614	53065;53066;53067	chr2:178591181;178591180;178591179	chr2:179455908;179455907;179455906
N2B	11117	33574;33575;33576	chr2:178591181;178591180;178591179	chr2:179455908;179455907;179455906
Novex-1	11242	33949;33950;33951	chr2:178591181;178591180;178591179	chr2:179455908;179455907;179455906
Novex-2	11309	34150;34151;34152	chr2:178591181;178591180;178591179	chr2:179455908;179455907;179455906
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Fn3-34
• Domain position: 12
• Structural Position: 13
• Q(SASA): 0.5303
• 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
L/M	None	None	1.0	N	0.663	0.274	0.552125808554	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
L/A	0.1629	likely_benign	0.1588	benign	-0.719	Destabilizing	0.999	D	0.73	prob.delet.	None	None	None	None	N
L/C	0.3981	ambiguous	0.4057	ambiguous	-0.599	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
L/D	0.4511	ambiguous	0.4668	ambiguous	-0.186	Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	N
L/E	0.2109	likely_benign	0.206	benign	-0.284	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
L/F	0.1547	likely_benign	0.1551	benign	-0.742	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
L/G	0.4481	ambiguous	0.4209	ambiguous	-0.889	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
L/H	0.173	likely_benign	0.1826	benign	-0.17	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	N
L/I	0.0796	likely_benign	0.0846	benign	-0.397	Destabilizing	0.999	D	0.445	neutral	None	None	None	None	N
L/K	0.2348	likely_benign	0.229	benign	-0.337	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
L/M	0.096	likely_benign	0.0877	benign	-0.331	Destabilizing	1.0	D	0.663	neutral	N	0.474584789	None	None	N
L/N	0.2718	likely_benign	0.2682	benign	-0.115	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
L/P	0.5781	likely_pathogenic	0.7017	pathogenic	-0.471	Destabilizing	1.0	D	0.828	deleterious	N	0.471217427	None	None	N
L/Q	0.1215	likely_benign	0.1178	benign	-0.374	Destabilizing	1.0	D	0.801	deleterious	N	0.505050932	None	None	N
L/R	0.1911	likely_benign	0.1997	benign	0.247	Stabilizing	1.0	D	0.825	deleterious	N	0.519441594	None	None	N
L/S	0.1618	likely_benign	0.1621	benign	-0.596	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
L/T	0.1	likely_benign	0.1023	benign	-0.585	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
L/V	0.0759	likely_benign	0.0768	benign	-0.471	Destabilizing	0.999	D	0.495	neutral	N	0.455507546	None	None	N
L/W	0.2581	likely_benign	0.2843	benign	-0.737	Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	N
L/Y	0.3552	ambiguous	0.3508	ambiguous	-0.48	Destabilizing	1.0	D	0.827	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.