TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9196	27811;27812;27813	chr2:178712336;178712335;178712334	chr2:179577063;179577062;179577061
N2AB	8879	26860;26861;26862	chr2:178712336;178712335;178712334	chr2:179577063;179577062;179577061
N2A	7952	24079;24080;24081	chr2:178712336;178712335;178712334	chr2:179577063;179577062;179577061
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: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Ig-77
• Domain position: 85
• Structural Position: 171
• Q(SASA): 0.4213
• 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
S/L	None	None	0.183	D	0.481	0.328	0.343101102393	gnomAD-4.0.0	8.40225E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.18751E-06	0	0
S/T	rs1350223598	None	0.183	N	0.325	0.136	0.248417906384	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
S/T	rs1350223598	None	0.183	N	0.325	0.136	0.248417906384	gnomAD-4.0.0	3.0448E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.61481E-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
S/A	0.0713	likely_benign	0.0773	benign	-0.585	Destabilizing	0.089	N	0.222	neutral	N	0.483846359	None	None	N
S/C	0.1434	likely_benign	0.1404	benign	-0.403	Destabilizing	0.983	D	0.551	neutral	None	None	None	None	N
S/D	0.2356	likely_benign	0.2346	benign	-0.669	Destabilizing	0.129	N	0.297	neutral	None	None	None	None	N
S/E	0.3088	likely_benign	0.3161	benign	-0.722	Destabilizing	0.001	N	0.109	neutral	None	None	None	None	N
S/F	0.1252	likely_benign	0.1312	benign	-1.036	Destabilizing	0.264	N	0.651	neutral	None	None	None	None	N
S/G	0.0893	likely_benign	0.0949	benign	-0.763	Destabilizing	0.228	N	0.283	neutral	None	None	None	None	N
S/H	0.2163	likely_benign	0.2205	benign	-1.359	Destabilizing	0.001	N	0.191	neutral	None	None	None	None	N
S/I	0.1133	likely_benign	0.1203	benign	-0.228	Destabilizing	0.593	D	0.669	neutral	None	None	None	None	N
S/K	0.4063	ambiguous	0.4125	ambiguous	-0.708	Destabilizing	0.129	N	0.294	neutral	None	None	None	None	N
S/L	0.0922	likely_benign	0.0956	benign	-0.228	Destabilizing	0.183	N	0.481	neutral	D	0.525306853	None	None	N
S/M	0.1668	likely_benign	0.1826	benign	0.255	Stabilizing	0.836	D	0.571	neutral	None	None	None	None	N
S/N	0.0923	likely_benign	0.0957	benign	-0.588	Destabilizing	0.129	N	0.327	neutral	None	None	None	None	N
S/P	0.373	ambiguous	0.3602	ambiguous	-0.317	Destabilizing	0.523	D	0.53	neutral	N	0.491140967	None	None	N
S/Q	0.312	likely_benign	0.323	benign	-0.905	Destabilizing	0.01	N	0.133	neutral	None	None	None	None	N
S/R	0.3264	likely_benign	0.3244	benign	-0.456	Destabilizing	0.264	N	0.456	neutral	None	None	None	None	N
S/T	0.069	likely_benign	0.0728	benign	-0.593	Destabilizing	0.183	N	0.325	neutral	N	0.473395165	None	None	N
S/V	0.1314	likely_benign	0.1442	benign	-0.317	Destabilizing	0.593	D	0.527	neutral	None	None	None	None	N
S/W	0.2842	likely_benign	0.2721	benign	-1.013	Destabilizing	0.983	D	0.603	neutral	None	None	None	None	N
S/Y	0.1396	likely_benign	0.1435	benign	-0.739	Destabilizing	0.01	N	0.345	neutral	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.