TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29148	87667;87668;87669	chr2:178557912;178557911;178557910	chr2:179422639;179422638;179422637
N2AB	27507	82744;82745;82746	chr2:178557912;178557911;178557910	chr2:179422639;179422638;179422637
N2A	26580	79963;79964;79965	chr2:178557912;178557911;178557910	chr2:179422639;179422638;179422637
N2B	20083	60472;60473;60474	chr2:178557912;178557911;178557910	chr2:179422639;179422638;179422637
Novex-1	20208	60847;60848;60849	chr2:178557912;178557911;178557910	chr2:179422639;179422638;179422637
Novex-2	20275	61048;61049;61050	chr2:178557912;178557911;178557910	chr2:179422639;179422638;179422637
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Fn3-100
• Domain position: 12
• Structural Position: 13
• Q(SASA): 0.3187
• 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
S/G	None	None	0.959	N	0.437	0.21	0.299086750705	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
S/A	0.0898	likely_benign	0.0879	benign	-0.532	Destabilizing	0.863	D	0.443	neutral	None	None	None	None	I
S/C	0.1093	likely_benign	0.1107	benign	-0.417	Destabilizing	0.077	N	0.287	neutral	D	0.525565064	None	None	I
S/D	0.3244	likely_benign	0.3189	benign	0.123	Stabilizing	0.997	D	0.437	neutral	None	None	None	None	I
S/E	0.4403	ambiguous	0.4477	ambiguous	0.088	Stabilizing	0.99	D	0.431	neutral	None	None	None	None	I
S/F	0.2164	likely_benign	0.2235	benign	-0.853	Destabilizing	0.1	N	0.29	neutral	None	None	None	None	I
S/G	0.0914	likely_benign	0.0819	benign	-0.738	Destabilizing	0.959	D	0.437	neutral	N	0.475386959	None	None	I
S/H	0.3214	likely_benign	0.3218	benign	-1.241	Destabilizing	0.991	D	0.44	neutral	None	None	None	None	I
S/I	0.2209	likely_benign	0.2377	benign	-0.108	Destabilizing	0.976	D	0.493	neutral	N	0.464111173	None	None	I
S/K	0.6174	likely_pathogenic	0.6005	pathogenic	-0.607	Destabilizing	0.969	D	0.433	neutral	None	None	None	None	I
S/L	0.1134	likely_benign	0.1205	benign	-0.108	Destabilizing	0.884	D	0.481	neutral	None	None	None	None	I
S/M	0.1803	likely_benign	0.196	benign	0.074	Stabilizing	0.997	D	0.431	neutral	None	None	None	None	I
S/N	0.1321	likely_benign	0.1242	benign	-0.476	Destabilizing	0.996	D	0.479	neutral	N	0.492548568	None	None	I
S/P	0.77	likely_pathogenic	0.8067	pathogenic	-0.216	Destabilizing	0.997	D	0.461	neutral	None	None	None	None	I
S/Q	0.4581	ambiguous	0.4583	ambiguous	-0.63	Destabilizing	0.997	D	0.459	neutral	None	None	None	None	I
S/R	0.528	ambiguous	0.5135	ambiguous	-0.5	Destabilizing	0.996	D	0.459	neutral	N	0.494548723	None	None	I
S/T	0.0771	likely_benign	0.0782	benign	-0.529	Destabilizing	0.959	D	0.468	neutral	N	0.414084998	None	None	I
S/V	0.205	likely_benign	0.2248	benign	-0.216	Destabilizing	0.939	D	0.505	neutral	None	None	None	None	I
S/W	0.3427	ambiguous	0.365	ambiguous	-0.843	Destabilizing	0.999	D	0.526	neutral	None	None	None	None	I
S/Y	0.1966	likely_benign	0.2058	benign	-0.57	Destabilizing	0.321	N	0.289	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.