TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6323	19192;19193;19194	chr2:178729071;178729070;178729069	chr2:179593798;179593797;179593796
N2AB	6006	18241;18242;18243	chr2:178729071;178729070;178729069	chr2:179593798;179593797;179593796
N2A	5079	15460;15461;15462	chr2:178729071;178729070;178729069	chr2:179593798;179593797;179593796
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: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-47
• Domain position: 32
• Structural Position: 46
• Q(SASA): 0.2368
• 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
I/L	rs2079899039	None	0.004	D	0.399	0.084	0.424194796918	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
I/L	rs2079899039	None	0.004	D	0.399	0.084	0.424194796918	gnomAD-4.0.0	1.86043E-06	None	None	None	None	I	None	2.67108E-05	0	None	0	0	None	0	0	0	0	1.60246E-05

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	0.5172	ambiguous	0.5211	ambiguous	-2.12	Highly Destabilizing	0.035	N	0.529	neutral	None	None	None	None	I
I/C	0.7495	likely_pathogenic	0.7495	pathogenic	-1.355	Destabilizing	0.824	D	0.685	prob.neutral	None	None	None	None	I
I/D	0.9725	likely_pathogenic	0.9661	pathogenic	-1.778	Destabilizing	0.555	D	0.775	deleterious	None	None	None	None	I
I/E	0.9442	likely_pathogenic	0.9338	pathogenic	-1.605	Destabilizing	0.555	D	0.771	deleterious	None	None	None	None	I
I/F	0.2596	likely_benign	0.2691	benign	-1.25	Destabilizing	0.38	N	0.599	neutral	None	None	None	None	I
I/G	0.8692	likely_pathogenic	0.8592	pathogenic	-2.626	Highly Destabilizing	0.149	N	0.755	deleterious	None	None	None	None	I
I/H	0.8988	likely_pathogenic	0.8828	pathogenic	-1.977	Destabilizing	0.935	D	0.801	deleterious	None	None	None	None	I
I/K	0.8764	likely_pathogenic	0.8521	pathogenic	-1.384	Destabilizing	0.117	N	0.771	deleterious	D	0.546955578	None	None	I
I/L	0.1454	likely_benign	0.1456	benign	-0.698	Destabilizing	0.004	N	0.399	neutral	D	0.525829714	None	None	I
I/M	0.1379	likely_benign	0.142	benign	-0.614	Destabilizing	0.004	N	0.439	neutral	N	0.506948407	None	None	I
I/N	0.7768	likely_pathogenic	0.7533	pathogenic	-1.523	Destabilizing	0.555	D	0.795	deleterious	None	None	None	None	I
I/P	0.9069	likely_pathogenic	0.8958	pathogenic	-1.147	Destabilizing	0.791	D	0.787	deleterious	None	None	None	None	I
I/Q	0.8864	likely_pathogenic	0.8707	pathogenic	-1.454	Destabilizing	0.38	N	0.803	deleterious	None	None	None	None	I
I/R	0.8272	likely_pathogenic	0.8041	pathogenic	-1.103	Destabilizing	0.317	N	0.797	deleterious	N	0.520457532	None	None	I
I/S	0.6728	likely_pathogenic	0.65	pathogenic	-2.291	Highly Destabilizing	0.081	N	0.723	prob.delet.	None	None	None	None	I
I/T	0.4191	ambiguous	0.3617	ambiguous	-1.969	Destabilizing	0.002	N	0.423	neutral	D	0.528344344	None	None	I
I/V	0.0532	likely_benign	0.0557	benign	-1.147	Destabilizing	None	N	0.199	neutral	N	0.396003456	None	None	I
I/W	0.9305	likely_pathogenic	0.9232	pathogenic	-1.528	Destabilizing	0.935	D	0.796	deleterious	None	None	None	None	I
I/Y	0.7683	likely_pathogenic	0.7702	pathogenic	-1.224	Destabilizing	0.555	D	0.709	prob.delet.	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.