TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14021	42286;42287;42288	chr2:178634813;178634812;178634811	chr2:179499540;179499539;179499538
N2AB	12380	37363;37364;37365	chr2:178634813;178634812;178634811	chr2:179499540;179499539;179499538
N2A	11453	34582;34583;34584	chr2:178634813;178634812;178634811	chr2:179499540;179499539;179499538
N2B	4956	15091;15092;15093	chr2:178634813;178634812;178634811	chr2:179499540;179499539;179499538
Novex-1	5081	15466;15467;15468	chr2:178634813;178634812;178634811	chr2:179499540;179499539;179499538
Novex-2	5148	15667;15668;15669	chr2:178634813;178634812;178634811	chr2:179499540;179499539;179499538
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTA
• RefSeq wild type template codon: AAT
• Domain: Ig-90
• Domain position: 57
• Structural Position: 138
• Q(SASA): 0.0657
• 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/F	None	None	0.999	D	0.811	0.544	0.620476206791	gnomAD-4.0.0	6.8478E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.16347E-05	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	0.9881	likely_pathogenic	0.9759	pathogenic	-2.361	Highly Destabilizing	0.998	D	0.698	prob.delet.	None	None	None	None	N
L/C	0.9615	likely_pathogenic	0.9283	pathogenic	-1.624	Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	N
L/D	1.0	likely_pathogenic	0.9999	pathogenic	-2.854	Highly Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
L/E	0.9996	likely_pathogenic	0.9992	pathogenic	-2.537	Highly Destabilizing	0.999	D	0.843	deleterious	None	None	None	None	N
L/F	0.9718	likely_pathogenic	0.9201	pathogenic	-1.41	Destabilizing	0.999	D	0.811	deleterious	D	0.646994493	None	None	N
L/G	0.9977	likely_pathogenic	0.9957	pathogenic	-2.983	Highly Destabilizing	0.999	D	0.824	deleterious	None	None	None	None	N
L/H	0.999	likely_pathogenic	0.9975	pathogenic	-2.686	Highly Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
L/I	0.8387	likely_pathogenic	0.642	pathogenic	-0.515	Destabilizing	0.997	D	0.545	neutral	D	0.644973724	None	None	N
L/K	0.9992	likely_pathogenic	0.9983	pathogenic	-1.752	Destabilizing	0.999	D	0.861	deleterious	None	None	None	None	N
L/M	0.874	likely_pathogenic	0.6709	pathogenic	-0.601	Destabilizing	0.999	D	0.772	deleterious	None	None	None	None	N
L/N	0.9996	likely_pathogenic	0.9991	pathogenic	-2.386	Highly Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
L/P	0.9998	likely_pathogenic	0.9994	pathogenic	-1.117	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
L/Q	0.9982	likely_pathogenic	0.9951	pathogenic	-2.042	Highly Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
L/R	0.9973	likely_pathogenic	0.9953	pathogenic	-1.855	Destabilizing	0.999	D	0.863	deleterious	None	None	None	None	N
L/S	0.9995	likely_pathogenic	0.9985	pathogenic	-3.04	Highly Destabilizing	0.999	D	0.867	deleterious	D	0.650902661	None	None	N
L/T	0.9976	likely_pathogenic	0.9941	pathogenic	-2.546	Highly Destabilizing	0.999	D	0.811	deleterious	None	None	None	None	N
L/V	0.8805	likely_pathogenic	0.6822	pathogenic	-1.117	Destabilizing	0.997	D	0.545	neutral	D	0.647752835	None	None	N
L/W	0.9989	likely_pathogenic	0.9965	pathogenic	-1.834	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	N
L/Y	0.9983	likely_pathogenic	0.9956	pathogenic	-1.512	Destabilizing	0.999	D	0.813	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.