TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5001	15226;15227;15228	chr2:178734923;178734922;178734921	chr2:179599650;179599649;179599648
N2AB	4684	14275;14276;14277	chr2:178734923;178734922;178734921	chr2:179599650;179599649;179599648
N2A	3757	11494;11495;11496	chr2:178734923;178734922;178734921	chr2:179599650;179599649;179599648
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-33
• Domain position: 21
• Structural Position: 30
• Q(SASA): 0.25
• 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	N	0.801	0.386	0.567678221081	gnomAD-4.0.0	4.78956E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.60072E-06	0	0
L/V	rs774593495	-1.294	0.992	D	0.701	0.54	0.68230992181	gnomAD-2.1.1	4.11E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.15E-06	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	0.9408	likely_pathogenic	0.9521	pathogenic	-2.578	Highly Destabilizing	0.997	D	0.767	deleterious	None	None	None	None	N
L/C	0.9186	likely_pathogenic	0.9332	pathogenic	-1.754	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
L/D	0.9989	likely_pathogenic	0.9988	pathogenic	-3.281	Highly Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
L/E	0.9916	likely_pathogenic	0.9921	pathogenic	-3.004	Highly Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
L/F	0.1578	likely_benign	0.237	benign	-1.693	Destabilizing	0.999	D	0.801	deleterious	N	0.508756336	None	None	N
L/G	0.9855	likely_pathogenic	0.9868	pathogenic	-3.114	Highly Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
L/H	0.9457	likely_pathogenic	0.955	pathogenic	-2.644	Highly Destabilizing	1.0	D	0.823	deleterious	D	0.815585471	None	None	N
L/I	0.1599	likely_benign	0.1913	benign	-0.98	Destabilizing	0.992	D	0.691	prob.neutral	D	0.589167828	None	None	N
L/K	0.9832	likely_pathogenic	0.984	pathogenic	-2.024	Highly Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
L/M	0.2112	likely_benign	0.2582	benign	-0.94	Destabilizing	0.985	D	0.632	neutral	None	None	None	None	N
L/N	0.9917	likely_pathogenic	0.9926	pathogenic	-2.583	Highly Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
L/P	0.9954	likely_pathogenic	0.9948	pathogenic	-1.502	Destabilizing	1.0	D	0.837	deleterious	D	0.815585471	None	None	N
L/Q	0.9449	likely_pathogenic	0.9528	pathogenic	-2.36	Highly Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
L/R	0.9635	likely_pathogenic	0.9642	pathogenic	-1.941	Destabilizing	0.999	D	0.841	deleterious	D	0.815585471	None	None	N
L/S	0.9847	likely_pathogenic	0.9878	pathogenic	-3.153	Highly Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
L/T	0.9653	likely_pathogenic	0.9737	pathogenic	-2.724	Highly Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
L/V	0.2538	likely_benign	0.3087	benign	-1.502	Destabilizing	0.992	D	0.701	prob.neutral	D	0.690848973	None	None	N
L/W	0.7024	likely_pathogenic	0.772	pathogenic	-2.07	Highly Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
L/Y	0.7302	likely_pathogenic	0.7906	pathogenic	-1.786	Destabilizing	1.0	D	0.797	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.