TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21031	63316;63317;63318	chr2:178588634;178588633;178588632	chr2:179453361;179453360;179453359
N2AB	19390	58393;58394;58395	chr2:178588634;178588633;178588632	chr2:179453361;179453360;179453359
N2A	18463	55612;55613;55614	chr2:178588634;178588633;178588632	chr2:179453361;179453360;179453359
N2B	11966	36121;36122;36123	chr2:178588634;178588633;178588632	chr2:179453361;179453360;179453359
Novex-1	12091	36496;36497;36498	chr2:178588634;178588633;178588632	chr2:179453361;179453360;179453359
Novex-2	12158	36697;36698;36699	chr2:178588634;178588633;178588632	chr2:179453361;179453360;179453359
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Fn3-40
• Domain position: 69
• Structural Position: 100
• Q(SASA): 0.8053
• 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/Y	None	None	0.56	N	0.535	0.25	0.512883945787	gnomAD-4.0.0	1.6129E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.47671E-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
D/A	0.1295	likely_benign	0.1413	benign	-0.388	Destabilizing	0.005	N	0.445	neutral	N	0.436268424	None	None	N
D/C	0.3496	ambiguous	0.3855	ambiguous	-0.224	Destabilizing	0.864	D	0.517	neutral	None	None	None	None	N
D/E	0.1327	likely_benign	0.1311	benign	-0.363	Destabilizing	0.024	N	0.3	neutral	N	0.457278414	None	None	N
D/F	0.4119	ambiguous	0.4366	ambiguous	-0.266	Destabilizing	0.628	D	0.538	neutral	None	None	None	None	N
D/G	0.0559	likely_benign	0.0614	benign	-0.622	Destabilizing	None	N	0.222	neutral	N	0.322667986	None	None	N
D/H	0.2008	likely_benign	0.2077	benign	-0.265	Destabilizing	0.295	N	0.478	neutral	N	0.458990568	None	None	N
D/I	0.3901	ambiguous	0.4107	ambiguous	0.196	Stabilizing	0.356	N	0.56	neutral	None	None	None	None	N
D/K	0.3469	ambiguous	0.3149	benign	-0.331	Destabilizing	0.031	N	0.475	neutral	None	None	None	None	N
D/L	0.2716	likely_benign	0.2813	benign	0.196	Stabilizing	0.072	N	0.549	neutral	None	None	None	None	N
D/M	0.4534	ambiguous	0.4608	ambiguous	0.32	Stabilizing	0.628	D	0.522	neutral	None	None	None	None	N
D/N	0.0709	likely_benign	0.0722	benign	-0.404	Destabilizing	None	N	0.166	neutral	N	0.380529784	None	None	N
D/P	0.8033	likely_pathogenic	0.7751	pathogenic	0.024	Stabilizing	0.136	N	0.512	neutral	None	None	None	None	N
D/Q	0.2391	likely_benign	0.2354	benign	-0.347	Destabilizing	0.136	N	0.415	neutral	None	None	None	None	N
D/R	0.3452	ambiguous	0.3314	benign	-0.064	Destabilizing	0.136	N	0.529	neutral	None	None	None	None	N
D/S	0.0865	likely_benign	0.0892	benign	-0.615	Destabilizing	0.007	N	0.247	neutral	None	None	None	None	N
D/T	0.1995	likely_benign	0.2058	benign	-0.448	Destabilizing	0.031	N	0.481	neutral	None	None	None	None	N
D/V	0.2612	likely_benign	0.2762	benign	0.024	Stabilizing	0.106	N	0.555	neutral	N	0.514345205	None	None	N
D/W	0.7214	likely_pathogenic	0.7296	pathogenic	-0.171	Destabilizing	0.864	D	0.523	neutral	None	None	None	None	N
D/Y	0.1592	likely_benign	0.1692	benign	-0.077	Destabilizing	0.56	D	0.535	neutral	N	0.438057935	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.