TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8507	25744;25745;25746	chr2:178717215;178717214;178717213	chr2:179581942;179581941;179581940
N2AB	8190	24793;24794;24795	chr2:178717215;178717214;178717213	chr2:179581942;179581941;179581940
N2A	7263	22012;22013;22014	chr2:178717215;178717214;178717213	chr2:179581942;179581941;179581940
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: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Ig-70
• Domain position: 52
• Structural Position: 130
• Q(SASA): 0.4418
• 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
V/I	None	None	None	N	0.222	0.136	0.517322629239	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
V/A	0.1103	likely_benign	0.1144	benign	-0.445	Destabilizing	0.009	N	0.278	neutral	N	0.482668009	None	None	N
V/C	0.7809	likely_pathogenic	0.809	pathogenic	-0.538	Destabilizing	0.826	D	0.316	neutral	None	None	None	None	N
V/D	0.2087	likely_benign	0.2156	benign	-0.455	Destabilizing	0.067	N	0.381	neutral	None	None	None	None	N
V/E	0.158	likely_benign	0.1639	benign	-0.586	Destabilizing	None	N	0.185	neutral	N	0.465503614	None	None	N
V/F	0.1392	likely_benign	0.1479	benign	-0.76	Destabilizing	0.274	N	0.371	neutral	None	None	None	None	N
V/G	0.1631	likely_benign	0.1715	benign	-0.558	Destabilizing	0.127	N	0.38	neutral	N	0.517743375	None	None	N
V/H	0.3842	ambiguous	0.3962	ambiguous	-0.181	Destabilizing	0.625	D	0.402	neutral	None	None	None	None	N
V/I	0.0787	likely_benign	0.0799	benign	-0.301	Destabilizing	None	N	0.222	neutral	N	0.506603662	None	None	N
V/K	0.2487	likely_benign	0.2667	benign	-0.441	Destabilizing	0.001	N	0.248	neutral	None	None	None	None	N
V/L	0.1436	likely_benign	0.1485	benign	-0.301	Destabilizing	None	N	0.246	neutral	N	0.465045041	None	None	N
V/M	0.1225	likely_benign	0.1282	benign	-0.274	Destabilizing	0.007	N	0.223	neutral	None	None	None	None	N
V/N	0.1985	likely_benign	0.2051	benign	-0.152	Destabilizing	0.026	N	0.469	neutral	None	None	None	None	N
V/P	0.6503	likely_pathogenic	0.6994	pathogenic	-0.314	Destabilizing	0.051	N	0.428	neutral	None	None	None	None	N
V/Q	0.1947	likely_benign	0.2064	benign	-0.436	Destabilizing	0.035	N	0.439	neutral	None	None	None	None	N
V/R	0.2175	likely_benign	0.2359	benign	0.117	Stabilizing	0.051	N	0.433	neutral	None	None	None	None	N
V/S	0.1346	likely_benign	0.1371	benign	-0.461	Destabilizing	0.028	N	0.327	neutral	None	None	None	None	N
V/T	0.1163	likely_benign	0.1182	benign	-0.498	Destabilizing	None	N	0.199	neutral	None	None	None	None	N
V/W	0.6462	likely_pathogenic	0.6795	pathogenic	-0.84	Destabilizing	0.959	D	0.435	neutral	None	None	None	None	N
V/Y	0.4773	ambiguous	0.5045	ambiguous	-0.538	Destabilizing	0.433	N	0.345	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.