TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29379	88360;88361;88362	chr2:178557019;178557018;178557017	chr2:179421746;179421745;179421744
N2AB	27738	83437;83438;83439	chr2:178557019;178557018;178557017	chr2:179421746;179421745;179421744
N2A	26811	80656;80657;80658	chr2:178557019;178557018;178557017	chr2:179421746;179421745;179421744
N2B	20314	61165;61166;61167	chr2:178557019;178557018;178557017	chr2:179421746;179421745;179421744
Novex-1	20439	61540;61541;61542	chr2:178557019;178557018;178557017	chr2:179421746;179421745;179421744
Novex-2	20506	61741;61742;61743	chr2:178557019;178557018;178557017	chr2:179421746;179421745;179421744
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-102
• Domain position: 45
• Structural Position: 60
• Q(SASA): 0.3015
• 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
D/N	rs1285049057	-0.071	0.005	N	0.104	0.168	0.236890367714	gnomAD-2.1.1	6.37E-05	None	None	None	None	N	None	2.29516E-04	0	None	0	0	None	0	None	0	0	0
D/N	rs1285049057	-0.071	0.005	N	0.104	0.168	0.236890367714	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	7.24E-05	0	0	0	0	None	0	0	0	0	0
D/N	rs1285049057	-0.071	0.005	N	0.104	0.168	0.236890367714	gnomAD-4.0.0	7.68677E-06	None	None	None	None	N	None	1.01458E-04	0	None	0	0	None	0	0	0	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
D/A	0.1193	likely_benign	0.0953	benign	0.086	Stabilizing	0.051	N	0.209	neutral	N	0.494161934	None	None	N
D/C	0.4954	ambiguous	0.4183	ambiguous	-0.184	Destabilizing	0.998	D	0.371	neutral	None	None	None	None	N
D/E	0.1099	likely_benign	0.0994	benign	-0.419	Destabilizing	0.625	D	0.277	neutral	N	0.444386475	None	None	N
D/F	0.4829	ambiguous	0.3857	ambiguous	-0.047	Destabilizing	0.991	D	0.383	neutral	None	None	None	None	N
D/G	0.1241	likely_benign	0.1034	benign	-0.01	Destabilizing	0.454	N	0.315	neutral	N	0.447272064	None	None	N
D/H	0.2096	likely_benign	0.1716	benign	0.597	Stabilizing	0.966	D	0.289	neutral	N	0.472471648	None	None	N
D/I	0.2896	likely_benign	0.2207	benign	0.267	Stabilizing	0.974	D	0.419	neutral	None	None	None	None	N
D/K	0.2463	likely_benign	0.2067	benign	0.425	Stabilizing	0.067	N	0.206	neutral	None	None	None	None	N
D/L	0.2758	likely_benign	0.2264	benign	0.267	Stabilizing	0.842	D	0.371	neutral	None	None	None	None	N
D/M	0.4409	ambiguous	0.3783	ambiguous	0.013	Stabilizing	0.998	D	0.363	neutral	None	None	None	None	N
D/N	0.0798	likely_benign	0.0714	benign	0.189	Stabilizing	0.005	N	0.104	neutral	N	0.457086413	None	None	N
D/P	0.6167	likely_pathogenic	0.5572	ambiguous	0.225	Stabilizing	0.974	D	0.34	neutral	None	None	None	None	N
D/Q	0.2221	likely_benign	0.1947	benign	0.179	Stabilizing	0.949	D	0.305	neutral	None	None	None	None	N
D/R	0.2952	likely_benign	0.2495	benign	0.649	Stabilizing	0.728	D	0.339	neutral	None	None	None	None	N
D/S	0.0943	likely_benign	0.0823	benign	0.111	Stabilizing	0.172	N	0.189	neutral	None	None	None	None	N
D/T	0.1658	likely_benign	0.1401	benign	0.192	Stabilizing	0.728	D	0.279	neutral	None	None	None	None	N
D/V	0.1749	likely_benign	0.1361	benign	0.225	Stabilizing	0.801	D	0.363	neutral	N	0.470269602	None	None	N
D/W	0.812	likely_pathogenic	0.7434	pathogenic	-0.032	Destabilizing	0.998	D	0.471	neutral	None	None	None	None	N
D/Y	0.1995	likely_benign	0.1585	benign	0.173	Stabilizing	0.989	D	0.38	neutral	N	0.500237142	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.