TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31623	95092;95093;95094	chr2:178546464;178546463;178546462	chr2:179411191;179411190;179411189
N2AB	29982	90169;90170;90171	chr2:178546464;178546463;178546462	chr2:179411191;179411190;179411189
N2A	29055	87388;87389;87390	chr2:178546464;178546463;178546462	chr2:179411191;179411190;179411189
N2B	22558	67897;67898;67899	chr2:178546464;178546463;178546462	chr2:179411191;179411190;179411189
Novex-1	22683	68272;68273;68274	chr2:178546464;178546463;178546462	chr2:179411191;179411190;179411189
Novex-2	22750	68473;68474;68475	chr2:178546464;178546463;178546462	chr2:179411191;179411190;179411189
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: Ig-152
• Domain position: 3
• Structural Position: 9
• Q(SASA): 0.532
• 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/G	None	None	0.645	N	0.546	0.477	0.39208347742	gnomAD-4.0.0	6.84334E-07	None	None	None	None	N	None	0	0	None	0	2.5227E-05	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	0.2137	likely_benign	0.2152	benign	0.105	Stabilizing	0.477	N	0.546	neutral	D	0.529680883	None	None	N
D/C	0.6466	likely_pathogenic	0.6652	pathogenic	-0.179	Destabilizing	0.995	D	0.729	prob.delet.	None	None	None	None	N
D/E	0.1253	likely_benign	0.1322	benign	-0.375	Destabilizing	0.002	N	0.255	neutral	N	0.432284835	None	None	N
D/F	0.6426	likely_pathogenic	0.6581	pathogenic	-0.025	Destabilizing	0.981	D	0.739	prob.delet.	None	None	None	None	N
D/G	0.1801	likely_benign	0.1797	benign	0.013	Stabilizing	0.645	D	0.546	neutral	N	0.503126973	None	None	N
D/H	0.3139	likely_benign	0.3266	benign	0.622	Stabilizing	0.98	D	0.643	neutral	D	0.540975312	None	None	N
D/I	0.3973	ambiguous	0.4259	ambiguous	0.277	Stabilizing	0.945	D	0.745	deleterious	None	None	None	None	N
D/K	0.3576	ambiguous	0.3778	ambiguous	0.435	Stabilizing	0.547	D	0.516	neutral	None	None	None	None	N
D/L	0.4034	ambiguous	0.4159	ambiguous	0.277	Stabilizing	0.894	D	0.737	prob.delet.	None	None	None	None	N
D/M	0.6016	likely_pathogenic	0.6206	pathogenic	0.016	Stabilizing	0.995	D	0.742	deleterious	None	None	None	None	N
D/N	0.1147	likely_benign	0.1205	benign	0.217	Stabilizing	0.645	D	0.523	neutral	N	0.483561804	None	None	N
D/P	0.4688	ambiguous	0.4753	ambiguous	0.238	Stabilizing	0.945	D	0.65	neutral	None	None	None	None	N
D/Q	0.2954	likely_benign	0.3072	benign	0.207	Stabilizing	0.809	D	0.537	neutral	None	None	None	None	N
D/R	0.4071	ambiguous	0.4216	ambiguous	0.652	Stabilizing	0.894	D	0.699	prob.neutral	None	None	None	None	N
D/S	0.1378	likely_benign	0.1372	benign	0.129	Stabilizing	0.547	D	0.48	neutral	None	None	None	None	N
D/T	0.2572	likely_benign	0.2656	benign	0.209	Stabilizing	0.894	D	0.585	neutral	None	None	None	None	N
D/V	0.2574	likely_benign	0.2685	benign	0.238	Stabilizing	0.864	D	0.731	prob.delet.	D	0.541148671	None	None	N
D/W	0.8739	likely_pathogenic	0.8738	pathogenic	-0.012	Destabilizing	0.995	D	0.707	prob.neutral	None	None	None	None	N
D/Y	0.296	likely_benign	0.3067	benign	0.196	Stabilizing	0.975	D	0.737	prob.delet.	N	0.504140931	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.