TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8096	24511;24512;24513	chr2:178718914;178718913;178718912	chr2:179583641;179583640;179583639
N2AB	7779	23560;23561;23562	chr2:178718914;178718913;178718912	chr2:179583641;179583640;179583639
N2A	6852	20779;20780;20781	chr2:178718914;178718913;178718912	chr2:179583641;179583640;179583639
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: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-66
• Domain position: 19
• Structural Position: 29
• Q(SASA): 0.2773
• 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
T/I	rs370271716	None	None	N	0.389	0.068	0.134241683229	gnomAD-4.0.0	6.84548E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99713E-07	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
T/A	0.1018	likely_benign	0.0939	benign	-0.94	Destabilizing	None	N	0.272	neutral	N	0.484498019	None	None	N
T/C	0.4757	ambiguous	0.4373	ambiguous	-0.622	Destabilizing	0.676	D	0.505	neutral	None	None	None	None	N
T/D	0.5277	ambiguous	0.4984	ambiguous	0.104	Stabilizing	0.072	N	0.473	neutral	None	None	None	None	N
T/E	0.3988	ambiguous	0.3765	ambiguous	0.137	Stabilizing	0.072	N	0.491	neutral	None	None	None	None	N
T/F	0.2559	likely_benign	0.2428	benign	-1.023	Destabilizing	0.214	N	0.537	neutral	None	None	None	None	N
T/G	0.3267	likely_benign	0.301	benign	-1.215	Destabilizing	0.016	N	0.485	neutral	None	None	None	None	N
T/H	0.2232	likely_benign	0.2253	benign	-1.372	Destabilizing	0.628	D	0.536	neutral	None	None	None	None	N
T/I	0.1453	likely_benign	0.1401	benign	-0.293	Destabilizing	None	N	0.389	neutral	N	0.458707535	None	None	N
T/K	0.1652	likely_benign	0.1659	benign	-0.556	Destabilizing	0.012	N	0.478	neutral	N	0.516027569	None	None	N
T/L	0.1061	likely_benign	0.101	benign	-0.293	Destabilizing	0.006	N	0.454	neutral	None	None	None	None	N
T/M	0.1036	likely_benign	0.0979	benign	-0.155	Destabilizing	0.214	N	0.515	neutral	None	None	None	None	N
T/N	0.1478	likely_benign	0.1448	benign	-0.625	Destabilizing	0.072	N	0.447	neutral	None	None	None	None	N
T/P	0.2376	likely_benign	0.2186	benign	-0.477	Destabilizing	None	N	0.403	neutral	N	0.512010023	None	None	N
T/Q	0.2245	likely_benign	0.2215	benign	-0.686	Destabilizing	0.214	N	0.537	neutral	None	None	None	None	N
T/R	0.1325	likely_benign	0.132	benign	-0.41	Destabilizing	None	N	0.329	neutral	N	0.478143971	None	None	N
T/S	0.1278	likely_benign	0.1195	benign	-0.985	Destabilizing	0.001	N	0.305	neutral	N	0.4894384	None	None	N
T/V	0.1394	likely_benign	0.1347	benign	-0.477	Destabilizing	0.006	N	0.433	neutral	None	None	None	None	N
T/W	0.6141	likely_pathogenic	0.5875	pathogenic	-0.944	Destabilizing	0.864	D	0.575	neutral	None	None	None	None	N
T/Y	0.2984	likely_benign	0.2875	benign	-0.69	Destabilizing	0.356	N	0.535	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.