TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17755	53488;53489;53490	chr2:178607425;178607424;178607423	chr2:179472152;179472151;179472150
N2AB	16114	48565;48566;48567	chr2:178607425;178607424;178607423	chr2:179472152;179472151;179472150
N2A	15187	45784;45785;45786	chr2:178607425;178607424;178607423	chr2:179472152;179472151;179472150
N2B	8690	26293;26294;26295	chr2:178607425;178607424;178607423	chr2:179472152;179472151;179472150
Novex-1	8815	26668;26669;26670	chr2:178607425;178607424;178607423	chr2:179472152;179472151;179472150
Novex-2	8882	26869;26870;26871	chr2:178607425;178607424;178607423	chr2:179472152;179472151;179472150
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-113
• Domain position: 79
• Structural Position: 169
• Q(SASA): 0.3197
• 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
A/V	rs777396852	0.161	1.0	N	0.719	0.436	0.659072316242	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.91E-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
A/C	0.6282	likely_pathogenic	0.5307	ambiguous	-0.617	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	I
A/D	0.8625	likely_pathogenic	0.6979	pathogenic	-0.127	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	I
A/E	0.8096	likely_pathogenic	0.6521	pathogenic	-0.163	Destabilizing	1.0	D	0.853	deleterious	N	0.512838988	None	None	I
A/F	0.6432	likely_pathogenic	0.5093	ambiguous	-0.539	Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	I
A/G	0.2957	likely_benign	0.1879	benign	-0.578	Destabilizing	1.0	D	0.623	neutral	N	0.493231336	None	None	I
A/H	0.8608	likely_pathogenic	0.765	pathogenic	-0.447	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	I
A/I	0.556	ambiguous	0.4283	ambiguous	-0.003	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	I
A/K	0.9013	likely_pathogenic	0.8056	pathogenic	-0.532	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	I
A/L	0.4536	ambiguous	0.3273	benign	-0.003	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	I
A/M	0.5443	ambiguous	0.4259	ambiguous	-0.297	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	I
A/N	0.8029	likely_pathogenic	0.6592	pathogenic	-0.378	Destabilizing	1.0	D	0.896	deleterious	None	None	None	None	I
A/P	0.9818	likely_pathogenic	0.9408	pathogenic	-0.089	Destabilizing	1.0	D	0.855	deleterious	D	0.529693335	None	None	I
A/Q	0.7475	likely_pathogenic	0.6239	pathogenic	-0.465	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	I
A/R	0.8473	likely_pathogenic	0.7244	pathogenic	-0.265	Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	I
A/S	0.1877	likely_benign	0.1494	benign	-0.739	Destabilizing	1.0	D	0.631	neutral	N	0.518071449	None	None	I
A/T	0.2113	likely_benign	0.1547	benign	-0.661	Destabilizing	1.0	D	0.763	deleterious	N	0.507547811	None	None	I
A/V	0.2819	likely_benign	0.2097	benign	-0.089	Destabilizing	1.0	D	0.719	prob.delet.	N	0.510222757	None	None	I
A/W	0.9492	likely_pathogenic	0.8937	pathogenic	-0.817	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	I
A/Y	0.8309	likely_pathogenic	0.7317	pathogenic	-0.385	Destabilizing	1.0	D	0.891	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.