TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20234	60925;60926;60927	chr2:178591025;178591024;178591023	chr2:179455752;179455751;179455750
N2AB	18593	56002;56003;56004	chr2:178591025;178591024;178591023	chr2:179455752;179455751;179455750
N2A	17666	53221;53222;53223	chr2:178591025;178591024;178591023	chr2:179455752;179455751;179455750
N2B	11169	33730;33731;33732	chr2:178591025;178591024;178591023	chr2:179455752;179455751;179455750
Novex-1	11294	34105;34106;34107	chr2:178591025;178591024;178591023	chr2:179455752;179455751;179455750
Novex-2	11361	34306;34307;34308	chr2:178591025;178591024;178591023	chr2:179455752;179455751;179455750
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-34
• Domain position: 64
• Structural Position: 94
• Q(SASA): 0.2915
• 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
P/S	None	None	0.689	N	0.266	0.253	0.219573609325	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	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
P/A	0.1105	likely_benign	0.1155	benign	-1.483	Destabilizing	0.835	D	0.551	neutral	N	0.478480406	None	None	N
P/C	0.4902	ambiguous	0.4952	ambiguous	-0.501	Destabilizing	1.0	D	0.766	deleterious	None	None	None	None	N
P/D	0.5482	ambiguous	0.5785	pathogenic	-1.795	Destabilizing	0.991	D	0.623	neutral	None	None	None	None	N
P/E	0.4017	ambiguous	0.4291	ambiguous	-1.808	Destabilizing	0.991	D	0.607	neutral	None	None	None	None	N
P/F	0.5495	ambiguous	0.5772	pathogenic	-1.282	Destabilizing	0.999	D	0.772	deleterious	None	None	None	None	N
P/G	0.3151	likely_benign	0.3418	ambiguous	-1.75	Destabilizing	0.97	D	0.63	neutral	None	None	None	None	N
P/H	0.2455	likely_benign	0.2605	benign	-1.525	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
P/I	0.3299	likely_benign	0.3431	ambiguous	-0.831	Destabilizing	0.991	D	0.773	deleterious	None	None	None	None	N
P/K	0.4031	ambiguous	0.4242	ambiguous	-1.344	Destabilizing	0.991	D	0.628	neutral	None	None	None	None	N
P/L	0.1502	likely_benign	0.1602	benign	-0.831	Destabilizing	0.961	D	0.677	prob.neutral	N	0.489948193	None	None	N
P/M	0.347	ambiguous	0.359	ambiguous	-0.434	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	N
P/N	0.3539	ambiguous	0.3737	ambiguous	-0.956	Destabilizing	0.991	D	0.681	prob.neutral	None	None	None	None	N
P/Q	0.2217	likely_benign	0.2336	benign	-1.156	Destabilizing	0.994	D	0.699	prob.neutral	N	0.4618948	None	None	N
P/R	0.28	likely_benign	0.2936	benign	-0.795	Destabilizing	0.994	D	0.745	deleterious	N	0.454083394	None	None	N
P/S	0.1313	likely_benign	0.1433	benign	-1.255	Destabilizing	0.689	D	0.266	neutral	N	0.387415684	None	None	N
P/T	0.1051	likely_benign	0.109	benign	-1.19	Destabilizing	0.248	N	0.266	neutral	N	0.382065793	None	None	N
P/V	0.2308	likely_benign	0.2379	benign	-1.019	Destabilizing	0.97	D	0.642	neutral	None	None	None	None	N
P/W	0.6588	likely_pathogenic	0.6843	pathogenic	-1.538	Destabilizing	1.0	D	0.728	prob.delet.	None	None	None	None	N
P/Y	0.4803	ambiguous	0.498	ambiguous	-1.28	Destabilizing	0.999	D	0.773	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.