TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31632	95119;95120;95121	chr2:178546437;178546436;178546435	chr2:179411164;179411163;179411162
N2AB	29991	90196;90197;90198	chr2:178546437;178546436;178546435	chr2:179411164;179411163;179411162
N2A	29064	87415;87416;87417	chr2:178546437;178546436;178546435	chr2:179411164;179411163;179411162
N2B	22567	67924;67925;67926	chr2:178546437;178546436;178546435	chr2:179411164;179411163;179411162
Novex-1	22692	68299;68300;68301	chr2:178546437;178546436;178546435	chr2:179411164;179411163;179411162
Novex-2	22759	68500;68501;68502	chr2:178546437;178546436;178546435	chr2:179411164;179411163;179411162
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-152
• Domain position: 12
• Structural Position: 26
• Q(SASA): 0.6672
• 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
D/A	None	None	1.0	N	0.729	0.493	0.282575091529	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	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
D/A	0.6032	likely_pathogenic	0.6176	pathogenic	-0.576	Destabilizing	1.0	D	0.729	prob.delet.	N	0.473679514	None	None	I
D/C	0.9295	likely_pathogenic	0.9284	pathogenic	-0.267	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	I
D/E	0.5909	likely_pathogenic	0.6158	pathogenic	-0.509	Destabilizing	1.0	D	0.433	neutral	N	0.475506311	None	None	I
D/F	0.9316	likely_pathogenic	0.9346	pathogenic	0.038	Stabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	I
D/G	0.7492	likely_pathogenic	0.768	pathogenic	-0.932	Destabilizing	1.0	D	0.707	prob.neutral	N	0.477114505	None	None	I
D/H	0.7428	likely_pathogenic	0.7531	pathogenic	-0.159	Destabilizing	1.0	D	0.667	neutral	N	0.454997779	None	None	I
D/I	0.8174	likely_pathogenic	0.8302	pathogenic	0.369	Stabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	I
D/K	0.9233	likely_pathogenic	0.936	pathogenic	-0.255	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	I
D/L	0.8298	likely_pathogenic	0.8447	pathogenic	0.369	Stabilizing	1.0	D	0.751	deleterious	None	None	None	None	I
D/M	0.9298	likely_pathogenic	0.938	pathogenic	0.739	Stabilizing	1.0	D	0.708	prob.delet.	None	None	None	None	I
D/N	0.2529	likely_benign	0.2585	benign	-0.862	Destabilizing	1.0	D	0.633	neutral	N	0.473986158	None	None	I
D/P	0.8872	likely_pathogenic	0.8868	pathogenic	0.079	Stabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	I
D/Q	0.855	likely_pathogenic	0.8717	pathogenic	-0.692	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	I
D/R	0.9216	likely_pathogenic	0.9333	pathogenic	-0.021	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	I
D/S	0.3558	ambiguous	0.3592	ambiguous	-1.076	Destabilizing	1.0	D	0.671	neutral	None	None	None	None	I
D/T	0.5839	likely_pathogenic	0.5931	pathogenic	-0.771	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	I
D/V	0.6276	likely_pathogenic	0.6444	pathogenic	0.079	Stabilizing	1.0	D	0.751	deleterious	N	0.470081848	None	None	I
D/W	0.9886	likely_pathogenic	0.9891	pathogenic	0.305	Stabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	I
D/Y	0.6813	likely_pathogenic	0.6921	pathogenic	0.3	Stabilizing	1.0	D	0.711	prob.delet.	N	0.466354084	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.