TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35631	107116;107117;107118	chr2:178528860;178528859;178528858	chr2:179393587;179393586;179393585
N2AB	33990	102193;102194;102195	chr2:178528860;178528859;178528858	chr2:179393587;179393586;179393585
N2A	33063	99412;99413;99414	chr2:178528860;178528859;178528858	chr2:179393587;179393586;179393585
N2B	26566	79921;79922;79923	chr2:178528860;178528859;178528858	chr2:179393587;179393586;179393585
Novex-1	26691	80296;80297;80298	chr2:178528860;178528859;178528858	chr2:179393587;179393586;179393585
Novex-2	26758	80497;80498;80499	chr2:178528860;178528859;178528858	chr2:179393587;179393586;179393585
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-167
• Domain position: 25
• Structural Position: 38
• Q(SASA): 0.7658
• 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
A/T	None	None	0.549	N	0.184	0.086	0.240491677333	gnomAD-4.0.0	1.36829E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.87287E-05	0	8.99395E-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
A/C	0.7041	likely_pathogenic	0.6824	pathogenic	-0.776	Destabilizing	0.992	D	0.311	neutral	None	None	None	None	N
A/D	0.2764	likely_benign	0.2613	benign	-0.396	Destabilizing	0.712	D	0.365	neutral	N	0.468450705	None	None	N
A/E	0.2327	likely_benign	0.2205	benign	-0.552	Destabilizing	0.617	D	0.354	neutral	None	None	None	None	N
A/F	0.4068	ambiguous	0.3781	ambiguous	-0.905	Destabilizing	0.85	D	0.361	neutral	None	None	None	None	N
A/G	0.21	likely_benign	0.197	benign	-0.233	Destabilizing	0.549	D	0.185	neutral	N	0.469144139	None	None	N
A/H	0.4867	ambiguous	0.4591	ambiguous	-0.245	Destabilizing	0.992	D	0.322	neutral	None	None	None	None	N
A/I	0.2663	likely_benign	0.2327	benign	-0.367	Destabilizing	0.005	N	0.179	neutral	None	None	None	None	N
A/K	0.3739	ambiguous	0.3616	ambiguous	-0.464	Destabilizing	0.617	D	0.357	neutral	None	None	None	None	N
A/L	0.2063	likely_benign	0.1806	benign	-0.367	Destabilizing	0.103	N	0.3	neutral	None	None	None	None	N
A/M	0.3052	likely_benign	0.2763	benign	-0.438	Destabilizing	0.85	D	0.302	neutral	None	None	None	None	N
A/N	0.3012	likely_benign	0.2814	benign	-0.184	Destabilizing	0.92	D	0.374	neutral	None	None	None	None	N
A/P	0.1596	likely_benign	0.1232	benign	-0.288	Destabilizing	0.002	N	0.103	neutral	N	0.431876616	None	None	N
A/Q	0.3219	likely_benign	0.2985	benign	-0.459	Destabilizing	0.92	D	0.326	neutral	None	None	None	None	N
A/R	0.3231	likely_benign	0.3133	benign	-0.029	Destabilizing	0.92	D	0.346	neutral	None	None	None	None	N
A/S	0.1071	likely_benign	0.1017	benign	-0.378	Destabilizing	0.549	D	0.22	neutral	N	0.466717122	None	None	N
A/T	0.102	likely_benign	0.0957	benign	-0.455	Destabilizing	0.549	D	0.184	neutral	N	0.467063839	None	None	N
A/V	0.1402	likely_benign	0.1259	benign	-0.288	Destabilizing	0.002	N	0.078	neutral	N	0.468797422	None	None	N
A/W	0.78	likely_pathogenic	0.7465	pathogenic	-1.013	Destabilizing	0.992	D	0.409	neutral	None	None	None	None	N
A/Y	0.5587	ambiguous	0.531	ambiguous	-0.672	Destabilizing	0.92	D	0.358	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.