TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3428	10507;10508;10509	chr2:178759005;178759004;178759003	chr2:179623732;179623731;179623730
N2AB	3428	10507;10508;10509	chr2:178759005;178759004;178759003	chr2:179623732;179623731;179623730
N2A	3428	10507;10508;10509	chr2:178759005;178759004;178759003	chr2:179623732;179623731;179623730
N2B	3382	10369;10370;10371	chr2:178759005;178759004;178759003	chr2:179623732;179623731;179623730
Novex-1	3382	10369;10370;10371	chr2:178759005;178759004;178759003	chr2:179623732;179623731;179623730
Novex-2	3382	10369;10370;10371	chr2:178759005;178759004;178759003	chr2:179623732;179623731;179623730
Novex-3	3428	10507;10508;10509	chr2:178759005;178759004;178759003	chr2:179623732;179623731;179623730

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-24
• Domain position: 84
• Structural Position: 171
• Q(SASA): 0.4702
• 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
T/I	None	None	0.994	N	0.707	0.41	0.655434838176	gnomAD-4.0.0	4.80131E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.25003E-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
T/A	0.0896	likely_benign	0.0979	benign	-0.711	Destabilizing	0.835	D	0.514	neutral	N	0.504414832	None	None	N
T/C	0.5619	ambiguous	0.551	ambiguous	-0.313	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
T/D	0.4695	ambiguous	0.5185	ambiguous	-0.187	Destabilizing	0.97	D	0.667	neutral	None	None	None	None	N
T/E	0.2905	likely_benign	0.3443	ambiguous	-0.25	Destabilizing	0.97	D	0.661	neutral	None	None	None	None	N
T/F	0.2998	likely_benign	0.2974	benign	-1.16	Destabilizing	0.999	D	0.805	deleterious	None	None	None	None	N
T/G	0.3372	likely_benign	0.3735	ambiguous	-0.867	Destabilizing	0.97	D	0.706	prob.neutral	None	None	None	None	N
T/H	0.2624	likely_benign	0.2859	benign	-1.28	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
T/I	0.198	likely_benign	0.2242	benign	-0.404	Destabilizing	0.994	D	0.707	prob.neutral	N	0.514569191	None	None	N
T/K	0.1717	likely_benign	0.1997	benign	-0.494	Destabilizing	0.961	D	0.663	neutral	N	0.494374704	None	None	N
T/L	0.1573	likely_benign	0.1635	benign	-0.404	Destabilizing	0.985	D	0.63	neutral	None	None	None	None	N
T/M	0.114	likely_benign	0.1105	benign	0.088	Stabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
T/N	0.182	likely_benign	0.1981	benign	-0.282	Destabilizing	0.97	D	0.557	neutral	None	None	None	None	N
T/P	0.2816	likely_benign	0.3574	ambiguous	-0.478	Destabilizing	0.994	D	0.707	prob.neutral	N	0.506995886	None	None	N
T/Q	0.2041	likely_benign	0.2408	benign	-0.614	Destabilizing	0.996	D	0.735	prob.delet.	None	None	None	None	N
T/R	0.1362	likely_benign	0.1497	benign	-0.187	Destabilizing	0.994	D	0.729	prob.delet.	N	0.508308856	None	None	N
T/S	0.1148	likely_benign	0.1149	benign	-0.525	Destabilizing	0.287	N	0.261	neutral	N	0.372714814	None	None	N
T/V	0.1516	likely_benign	0.1624	benign	-0.478	Destabilizing	0.985	D	0.505	neutral	None	None	None	None	N
T/W	0.6889	likely_pathogenic	0.7035	pathogenic	-1.074	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
T/Y	0.376	ambiguous	0.3899	ambiguous	-0.819	Destabilizing	0.999	D	0.814	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.