TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21317	64174;64175;64176	chr2:178587262;178587261;178587260	chr2:179451989;179451988;179451987
N2AB	19676	59251;59252;59253	chr2:178587262;178587261;178587260	chr2:179451989;179451988;179451987
N2A	18749	56470;56471;56472	chr2:178587262;178587261;178587260	chr2:179451989;179451988;179451987
N2B	12252	36979;36980;36981	chr2:178587262;178587261;178587260	chr2:179451989;179451988;179451987
Novex-1	12377	37354;37355;37356	chr2:178587262;178587261;178587260	chr2:179451989;179451988;179451987
Novex-2	12444	37555;37556;37557	chr2:178587262;178587261;178587260	chr2:179451989;179451988;179451987
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Fn3-42
• Domain position: 52
• Structural Position: 69
• Q(SASA): 0.1006
• 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	None	None	None	N	0.303	0.071	0.187945064343	gnomAD-4.0.0	1.59254E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43295E-05	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	0.0846	likely_benign	0.097	benign	-0.695	Destabilizing	None	N	0.201	neutral	N	0.454414254	None	None	N
T/C	0.2876	likely_benign	0.3342	benign	-0.472	Destabilizing	0.824	D	0.456	neutral	None	None	None	None	N
T/D	0.4792	ambiguous	0.5354	ambiguous	0.088	Stabilizing	0.081	N	0.459	neutral	None	None	None	None	N
T/E	0.3993	ambiguous	0.4931	ambiguous	0.161	Stabilizing	0.081	N	0.419	neutral	None	None	None	None	N
T/F	0.2197	likely_benign	0.2776	benign	-0.737	Destabilizing	0.38	N	0.507	neutral	None	None	None	None	N
T/G	0.287	likely_benign	0.3056	benign	-1.0	Destabilizing	0.081	N	0.448	neutral	None	None	None	None	N
T/H	0.2705	likely_benign	0.3239	benign	-1.174	Destabilizing	0.003	N	0.43	neutral	None	None	None	None	N
T/I	0.1293	likely_benign	0.1639	benign	0.038	Stabilizing	None	N	0.303	neutral	N	0.499415825	None	None	N
T/K	0.2892	likely_benign	0.3554	ambiguous	-0.347	Destabilizing	0.081	N	0.46	neutral	None	None	None	None	N
T/L	0.0848	likely_benign	0.1005	benign	0.038	Stabilizing	0.035	N	0.424	neutral	None	None	None	None	N
T/M	0.0785	likely_benign	0.0963	benign	-0.019	Destabilizing	0.38	N	0.476	neutral	None	None	None	None	N
T/N	0.1288	likely_benign	0.1424	benign	-0.593	Destabilizing	None	N	0.285	neutral	N	0.445253267	None	None	N
T/P	0.4099	ambiguous	0.4491	ambiguous	-0.173	Destabilizing	0.317	N	0.492	neutral	N	0.491124416	None	None	N
T/Q	0.2642	likely_benign	0.3257	benign	-0.54	Destabilizing	0.38	N	0.488	neutral	None	None	None	None	N
T/R	0.2729	likely_benign	0.3427	ambiguous	-0.329	Destabilizing	0.38	N	0.493	neutral	None	None	None	None	N
T/S	0.1042	likely_benign	0.1092	benign	-0.894	Destabilizing	None	N	0.179	neutral	N	0.456027621	None	None	N
T/V	0.1113	likely_benign	0.1337	benign	-0.173	Destabilizing	0.035	N	0.427	neutral	None	None	None	None	N
T/W	0.6176	likely_pathogenic	0.6979	pathogenic	-0.773	Destabilizing	0.935	D	0.518	neutral	None	None	None	None	N
T/Y	0.3041	likely_benign	0.3645	ambiguous	-0.444	Destabilizing	0.235	N	0.507	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.