TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26835	80728;80729;80730	chr2:178565629;178565628;178565627	chr2:179430356;179430355;179430354
N2AB	25194	75805;75806;75807	chr2:178565629;178565628;178565627	chr2:179430356;179430355;179430354
N2A	24267	73024;73025;73026	chr2:178565629;178565628;178565627	chr2:179430356;179430355;179430354
N2B	17770	53533;53534;53535	chr2:178565629;178565628;178565627	chr2:179430356;179430355;179430354
Novex-1	17895	53908;53909;53910	chr2:178565629;178565628;178565627	chr2:179430356;179430355;179430354
Novex-2	17962	54109;54110;54111	chr2:178565629;178565628;178565627	chr2:179430356;179430355;179430354
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Fn3-83
• Domain position: 56
• Structural Position: 88
• Q(SASA): 0.5398
• Predicted PPI site: I

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/A	rs1705503390	None	0.009	N	0.102	0.125	0.394685799254	gnomAD-4.0.0	1.59161E-06	None	None	None	None	I	None	0	0	None	0	2.77331E-05	None	0	0	0	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	0.1082	likely_benign	0.1119	benign	-1.101	Destabilizing	0.009	N	0.102	neutral	N	0.438807297	None	None	I
V/C	0.6281	likely_pathogenic	0.6532	pathogenic	-0.708	Destabilizing	0.979	D	0.353	neutral	None	None	None	None	I
V/D	0.2174	likely_benign	0.2213	benign	-0.701	Destabilizing	0.799	D	0.372	neutral	N	0.433265404	None	None	I
V/E	0.239	likely_benign	0.2415	benign	-0.697	Destabilizing	0.46	N	0.323	neutral	None	None	None	None	I
V/F	0.1276	likely_benign	0.1223	benign	-0.849	Destabilizing	0.955	D	0.373	neutral	N	0.509150029	None	None	I
V/G	0.1145	likely_benign	0.1218	benign	-1.374	Destabilizing	0.69	D	0.346	neutral	N	0.457547773	None	None	I
V/H	0.4151	ambiguous	0.4335	ambiguous	-0.687	Destabilizing	0.996	D	0.358	neutral	None	None	None	None	I
V/I	0.0723	likely_benign	0.0727	benign	-0.46	Destabilizing	0.094	N	0.315	neutral	N	0.452141953	None	None	I
V/K	0.3428	ambiguous	0.3631	ambiguous	-0.78	Destabilizing	0.65	D	0.319	neutral	None	None	None	None	I
V/L	0.1475	likely_benign	0.1552	benign	-0.46	Destabilizing	0.049	N	0.225	neutral	N	0.448101571	None	None	I
V/M	0.1191	likely_benign	0.1198	benign	-0.505	Destabilizing	0.984	D	0.368	neutral	None	None	None	None	I
V/N	0.117	likely_benign	0.13	benign	-0.661	Destabilizing	0.217	N	0.348	neutral	None	None	None	None	I
V/P	0.6455	likely_pathogenic	0.6523	pathogenic	-0.639	Destabilizing	0.359	N	0.329	neutral	None	None	None	None	I
V/Q	0.2759	likely_benign	0.2852	benign	-0.785	Destabilizing	0.904	D	0.375	neutral	None	None	None	None	I
V/R	0.3505	ambiguous	0.3623	ambiguous	-0.297	Destabilizing	0.933	D	0.38	neutral	None	None	None	None	I
V/S	0.101	likely_benign	0.1073	benign	-1.152	Destabilizing	0.307	N	0.308	neutral	None	None	None	None	I
V/T	0.1039	likely_benign	0.1075	benign	-1.03	Destabilizing	None	N	0.117	neutral	None	None	None	None	I
V/W	0.7468	likely_pathogenic	0.7357	pathogenic	-0.995	Destabilizing	0.999	D	0.38	neutral	None	None	None	None	I
V/Y	0.3724	ambiguous	0.3783	ambiguous	-0.686	Destabilizing	0.988	D	0.362	neutral	None	None	None	None	I

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.