TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7593	23002;23003;23004	chr2:178721886;178721885;178721884	chr2:179586613;179586612;179586611
N2AB	7276	22051;22052;22053	chr2:178721886;178721885;178721884	chr2:179586613;179586612;179586611
N2A	6349	19270;19271;19272	chr2:178721886;178721885;178721884	chr2:179586613;179586612;179586611
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: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-60
• Domain position: 79
• Structural Position: 163
• Q(SASA): 0.7794
• 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
V/A	rs758335261	0.002	0.011	N	0.248	0.125	0.306695030598	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
V/A	rs758335261	0.002	0.011	N	0.248	0.125	0.306695030598	gnomAD-4.0.0	1.59349E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86213E-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
V/A	0.0974	likely_benign	0.1006	benign	-0.282	Destabilizing	0.011	N	0.248	neutral	N	0.417213808	None	None	I
V/C	0.8098	likely_pathogenic	0.8036	pathogenic	-0.659	Destabilizing	0.999	D	0.557	neutral	None	None	None	None	I
V/D	0.4193	ambiguous	0.4412	ambiguous	-0.387	Destabilizing	0.984	D	0.628	neutral	N	0.498231312	None	None	I
V/E	0.3783	ambiguous	0.3914	ambiguous	-0.518	Destabilizing	0.976	D	0.555	neutral	None	None	None	None	I
V/F	0.1523	likely_benign	0.1644	benign	-0.713	Destabilizing	0.984	D	0.528	neutral	N	0.476147469	None	None	I
V/G	0.255	likely_benign	0.2619	benign	-0.341	Destabilizing	0.811	D	0.603	neutral	N	0.514108424	None	None	I
V/H	0.6475	likely_pathogenic	0.6626	pathogenic	0.031	Stabilizing	0.999	D	0.658	neutral	None	None	None	None	I
V/I	0.0861	likely_benign	0.0919	benign	-0.277	Destabilizing	0.896	D	0.469	neutral	N	0.498408253	None	None	I
V/K	0.585	likely_pathogenic	0.6046	pathogenic	-0.312	Destabilizing	0.976	D	0.559	neutral	None	None	None	None	I
V/L	0.2666	likely_benign	0.3091	benign	-0.277	Destabilizing	0.78	D	0.515	neutral	N	0.442322897	None	None	I
V/M	0.1508	likely_benign	0.1642	benign	-0.428	Destabilizing	0.996	D	0.497	neutral	None	None	None	None	I
V/N	0.3598	ambiguous	0.3723	ambiguous	-0.07	Destabilizing	0.988	D	0.644	neutral	None	None	None	None	I
V/P	0.9295	likely_pathogenic	0.9385	pathogenic	-0.249	Destabilizing	0.988	D	0.611	neutral	None	None	None	None	I
V/Q	0.4484	ambiguous	0.4563	ambiguous	-0.324	Destabilizing	0.988	D	0.621	neutral	None	None	None	None	I
V/R	0.4654	ambiguous	0.4792	ambiguous	0.178	Stabilizing	0.988	D	0.645	neutral	None	None	None	None	I
V/S	0.1738	likely_benign	0.1809	benign	-0.359	Destabilizing	0.851	D	0.561	neutral	None	None	None	None	I
V/T	0.1544	likely_benign	0.1645	benign	-0.4	Destabilizing	0.132	N	0.389	neutral	None	None	None	None	I
V/W	0.8252	likely_pathogenic	0.8319	pathogenic	-0.774	Destabilizing	0.999	D	0.697	prob.neutral	None	None	None	None	I
V/Y	0.603	likely_pathogenic	0.609	pathogenic	-0.479	Destabilizing	0.996	D	0.539	neutral	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.