TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7778	23557;23558;23559	chr2:178720430;178720429;178720428	chr2:179585157;179585156;179585155
N2AB	7461	22606;22607;22608	chr2:178720430;178720429;178720428	chr2:179585157;179585156;179585155
N2A	6534	19825;19826;19827	chr2:178720430;178720429;178720428	chr2:179585157;179585156;179585155
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: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-62
• Domain position: 77
• Structural Position: 161
• Q(SASA): 0.1565
• 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
N/D	rs2078170998	None	0.966	D	0.609	0.427	0.294918367191	gnomAD-4.0.0	3.18347E-06	None	None	None	None	I	None	0	0	None	0	5.54631E-05	None	0	0	0	0	0
N/S	None	None	0.905	N	0.56	0.484	0.219573609325	gnomAD-4.0.0	1.59179E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43349E-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
N/A	0.9937	likely_pathogenic	0.9946	pathogenic	-1.012	Destabilizing	0.667	D	0.734	prob.delet.	None	None	None	None	I
N/C	0.9814	likely_pathogenic	0.983	pathogenic	-0.197	Destabilizing	0.999	D	0.797	deleterious	None	None	None	None	I
N/D	0.98	likely_pathogenic	0.9763	pathogenic	-0.95	Destabilizing	0.966	D	0.609	neutral	D	0.559500657	None	None	I
N/E	0.9986	likely_pathogenic	0.9986	pathogenic	-0.858	Destabilizing	0.977	D	0.668	neutral	None	None	None	None	I
N/F	0.9997	likely_pathogenic	0.9997	pathogenic	-0.832	Destabilizing	0.993	D	0.789	deleterious	None	None	None	None	I
N/G	0.9817	likely_pathogenic	0.9844	pathogenic	-1.332	Destabilizing	0.991	D	0.549	neutral	None	None	None	None	I
N/H	0.985	likely_pathogenic	0.9847	pathogenic	-1.091	Destabilizing	0.987	D	0.72	prob.delet.	D	0.560768105	None	None	I
N/I	0.9976	likely_pathogenic	0.9973	pathogenic	-0.199	Destabilizing	0.987	D	0.795	deleterious	D	0.561021594	None	None	I
N/K	0.999	likely_pathogenic	0.9989	pathogenic	-0.312	Destabilizing	0.998	D	0.671	neutral	D	0.560261126	None	None	I
N/L	0.9879	likely_pathogenic	0.9877	pathogenic	-0.199	Destabilizing	0.981	D	0.782	deleterious	None	None	None	None	I
N/M	0.9947	likely_pathogenic	0.9947	pathogenic	0.319	Stabilizing	1.0	D	0.795	deleterious	None	None	None	None	I
N/P	0.9986	likely_pathogenic	0.9984	pathogenic	-0.442	Destabilizing	0.993	D	0.796	deleterious	None	None	None	None	I
N/Q	0.9983	likely_pathogenic	0.9984	pathogenic	-1.013	Destabilizing	0.995	D	0.727	prob.delet.	None	None	None	None	I
N/R	0.9981	likely_pathogenic	0.998	pathogenic	-0.274	Destabilizing	0.998	D	0.733	prob.delet.	None	None	None	None	I
N/S	0.6786	likely_pathogenic	0.6895	pathogenic	-0.952	Destabilizing	0.905	D	0.56	neutral	N	0.50680728	None	None	I
N/T	0.9524	likely_pathogenic	0.9495	pathogenic	-0.681	Destabilizing	0.936	D	0.661	neutral	D	0.533256101	None	None	I
N/V	0.9943	likely_pathogenic	0.9943	pathogenic	-0.442	Destabilizing	0.894	D	0.788	deleterious	None	None	None	None	I
N/W	0.9998	likely_pathogenic	0.9998	pathogenic	-0.569	Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	I
N/Y	0.9967	likely_pathogenic	0.9965	pathogenic	-0.354	Destabilizing	0.296	N	0.441	neutral	D	0.5494118	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.