TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5552	16879;16880;16881	chr2:178732315;178732314;178732313	chr2:179597042;179597041;179597040
N2AB	5235	15928;15929;15930	chr2:178732315;178732314;178732313	chr2:179597042;179597041;179597040
N2A	4308	13147;13148;13149	chr2:178732315;178732314;178732313	chr2:179597042;179597041;179597040
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: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Ig-39
• Domain position: 10
• Structural Position: 13
• Q(SASA): 0.4405
• 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
S/L	None	None	0.669	N	0.339	0.272	0.641217788028	gnomAD-4.0.0	1.59916E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.87325E-06	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
S/A	0.0851	likely_benign	0.0898	benign	-0.404	Destabilizing	0.454	N	0.315	neutral	N	0.484402563	None	None	N
S/C	0.1395	likely_benign	0.1361	benign	-0.319	Destabilizing	0.998	D	0.333	neutral	None	None	None	None	N
S/D	0.4637	ambiguous	0.4022	ambiguous	0.192	Stabilizing	0.842	D	0.257	neutral	None	None	None	None	N
S/E	0.4919	ambiguous	0.4338	ambiguous	0.128	Stabilizing	0.842	D	0.235	neutral	None	None	None	None	N
S/F	0.1689	likely_benign	0.1531	benign	-0.791	Destabilizing	0.904	D	0.437	neutral	None	None	None	None	N
S/G	0.1201	likely_benign	0.118	benign	-0.575	Destabilizing	0.842	D	0.232	neutral	None	None	None	None	N
S/H	0.358	ambiguous	0.3145	benign	-1.098	Destabilizing	0.949	D	0.342	neutral	None	None	None	None	N
S/I	0.1726	likely_benign	0.1548	benign	-0.079	Destabilizing	0.949	D	0.441	neutral	None	None	None	None	N
S/K	0.6338	likely_pathogenic	0.5473	ambiguous	-0.538	Destabilizing	0.842	D	0.23	neutral	None	None	None	None	N
S/L	0.092	likely_benign	0.0905	benign	-0.079	Destabilizing	0.669	D	0.339	neutral	N	0.489708936	None	None	N
S/M	0.202	likely_benign	0.2065	benign	0.123	Stabilizing	0.991	D	0.339	neutral	None	None	None	None	N
S/N	0.183	likely_benign	0.1629	benign	-0.3	Destabilizing	0.842	D	0.293	neutral	None	None	None	None	N
S/P	0.3239	likely_benign	0.2823	benign	-0.155	Destabilizing	0.966	D	0.356	neutral	N	0.497315805	None	None	N
S/Q	0.46	ambiguous	0.416	ambiguous	-0.516	Destabilizing	0.974	D	0.329	neutral	None	None	None	None	N
S/R	0.5389	ambiguous	0.4412	ambiguous	-0.389	Destabilizing	0.974	D	0.359	neutral	None	None	None	None	N
S/T	0.0731	likely_benign	0.0759	benign	-0.391	Destabilizing	0.007	N	0.092	neutral	N	0.476512828	None	None	N
S/V	0.1589	likely_benign	0.1555	benign	-0.155	Destabilizing	0.728	D	0.341	neutral	None	None	None	None	N
S/W	0.3195	likely_benign	0.2805	benign	-0.776	Destabilizing	0.993	D	0.437	neutral	None	None	None	None	N
S/Y	0.165	likely_benign	0.1431	benign	-0.509	Destabilizing	0.016	N	0.238	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.