TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1604	5035;5036;5037	chr2:178777153;178777152;178777151	chr2:179641880;179641879;179641878
N2AB	1604	5035;5036;5037	chr2:178777153;178777152;178777151	chr2:179641880;179641879;179641878
N2A	1604	5035;5036;5037	chr2:178777153;178777152;178777151	chr2:179641880;179641879;179641878
N2B	1558	4897;4898;4899	chr2:178777153;178777152;178777151	chr2:179641880;179641879;179641878
Novex-1	1558	4897;4898;4899	chr2:178777153;178777152;178777151	chr2:179641880;179641879;179641878
Novex-2	1558	4897;4898;4899	chr2:178777153;178777152;178777151	chr2:179641880;179641879;179641878
Novex-3	1604	5035;5036;5037	chr2:178777153;178777152;178777151	chr2:179641880;179641879;179641878

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-7
• Domain position: 49
• Structural Position: 121
• Q(SASA): 0.0584
• 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
I/V	rs1382643483	-1.584	0.219	N	0.164	0.185	0.541015953236	gnomAD-2.1.1	3.98E-06	None	None	None	None	N	None	0	2.89E-05	None	0	0	None	0	None	0	0	0
I/V	rs1382643483	-1.584	0.219	N	0.164	0.185	0.541015953236	gnomAD-4.0.0	1.59075E-06	None	None	None	None	N	None	0	2.28634E-05	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
I/A	0.9236	likely_pathogenic	0.8791	pathogenic	-2.414	Highly Destabilizing	0.985	D	0.598	neutral	None	None	None	None	N
I/C	0.9219	likely_pathogenic	0.8894	pathogenic	-1.717	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
I/D	0.995	likely_pathogenic	0.991	pathogenic	-2.876	Highly Destabilizing	0.999	D	0.823	deleterious	None	None	None	None	N
I/E	0.9846	likely_pathogenic	0.9735	pathogenic	-2.643	Highly Destabilizing	0.999	D	0.815	deleterious	None	None	None	None	N
I/F	0.3227	likely_benign	0.292	benign	-1.415	Destabilizing	0.994	D	0.661	neutral	N	0.505596981	None	None	N
I/G	0.982	likely_pathogenic	0.9696	pathogenic	-2.958	Highly Destabilizing	0.998	D	0.8	deleterious	None	None	None	None	N
I/H	0.9603	likely_pathogenic	0.9415	pathogenic	-2.434	Highly Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
I/K	0.9731	likely_pathogenic	0.9583	pathogenic	-2.072	Highly Destabilizing	0.998	D	0.805	deleterious	None	None	None	None	N
I/L	0.2728	likely_benign	0.2406	benign	-0.845	Destabilizing	0.817	D	0.351	neutral	N	0.503373505	None	None	N
I/M	0.2064	likely_benign	0.1761	benign	-0.768	Destabilizing	0.911	D	0.374	neutral	D	0.567178943	None	None	N
I/N	0.9042	likely_pathogenic	0.8587	pathogenic	-2.431	Highly Destabilizing	0.999	D	0.826	deleterious	D	0.676867863	None	None	N
I/P	0.9936	likely_pathogenic	0.9901	pathogenic	-1.349	Destabilizing	0.999	D	0.824	deleterious	None	None	None	None	N
I/Q	0.9661	likely_pathogenic	0.9472	pathogenic	-2.282	Highly Destabilizing	0.998	D	0.827	deleterious	None	None	None	None	N
I/R	0.9556	likely_pathogenic	0.9345	pathogenic	-1.804	Destabilizing	0.998	D	0.824	deleterious	None	None	None	None	N
I/S	0.9283	likely_pathogenic	0.8846	pathogenic	-3.075	Highly Destabilizing	0.997	D	0.738	prob.delet.	D	0.547590697	None	None	N
I/T	0.8878	likely_pathogenic	0.8204	pathogenic	-2.693	Highly Destabilizing	0.98	D	0.658	neutral	D	0.546292518	None	None	N
I/V	0.1804	likely_benign	0.1591	benign	-1.349	Destabilizing	0.219	N	0.164	neutral	N	0.490716192	None	None	N
I/W	0.9396	likely_pathogenic	0.9221	pathogenic	-1.826	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
I/Y	0.7605	likely_pathogenic	0.7185	pathogenic	-1.503	Destabilizing	0.999	D	0.757	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.