TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15683	47272;47273;47274	chr2:178618411;178618410;178618409	chr2:179483138;179483137;179483136
N2AB	14042	42349;42350;42351	chr2:178618411;178618410;178618409	chr2:179483138;179483137;179483136
N2A	13115	39568;39569;39570	chr2:178618411;178618410;178618409	chr2:179483138;179483137;179483136
N2B	6618	20077;20078;20079	chr2:178618411;178618410;178618409	chr2:179483138;179483137;179483136
Novex-1	6743	20452;20453;20454	chr2:178618411;178618410;178618409	chr2:179483138;179483137;179483136
Novex-2	6810	20653;20654;20655	chr2:178618411;178618410;178618409	chr2:179483138;179483137;179483136
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-1
• Domain position: 27
• Structural Position: 29
• Q(SASA): 0.5488
• 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
T/I	rs2057733530	None	0.627	N	0.363	0.13	0.279776271856	gnomAD-4.0.0	1.59398E-06	None	None	None	None	I	None	0	0	None	0	2.78878E-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
T/A	0.0742	likely_benign	0.0905	benign	-0.446	Destabilizing	0.09	N	0.349	neutral	N	0.454908369	None	None	I
T/C	0.301	likely_benign	0.395	ambiguous	-0.262	Destabilizing	0.944	D	0.37	neutral	None	None	None	None	I
T/D	0.1694	likely_benign	0.2184	benign	0.297	Stabilizing	0.241	N	0.359	neutral	None	None	None	None	I
T/E	0.1529	likely_benign	0.1849	benign	0.232	Stabilizing	0.241	N	0.353	neutral	None	None	None	None	I
T/F	0.1865	likely_benign	0.2443	benign	-0.885	Destabilizing	0.818	D	0.458	neutral	None	None	None	None	I
T/G	0.188	likely_benign	0.2411	benign	-0.596	Destabilizing	0.116	N	0.371	neutral	None	None	None	None	I
T/H	0.2007	likely_benign	0.2485	benign	-0.939	Destabilizing	0.818	D	0.429	neutral	None	None	None	None	I
T/I	0.162	likely_benign	0.229	benign	-0.167	Destabilizing	0.627	D	0.363	neutral	N	0.461923257	None	None	I
T/K	0.2372	likely_benign	0.2639	benign	-0.368	Destabilizing	0.241	N	0.347	neutral	None	None	None	None	I
T/L	0.0981	likely_benign	0.1296	benign	-0.167	Destabilizing	0.388	N	0.353	neutral	None	None	None	None	I
T/M	0.094	likely_benign	0.1244	benign	0.027	Stabilizing	0.981	D	0.35	neutral	None	None	None	None	I
T/N	0.0837	likely_benign	0.1045	benign	-0.141	Destabilizing	0.006	N	0.185	neutral	N	0.37515805	None	None	I
T/P	0.4221	ambiguous	0.4704	ambiguous	-0.23	Destabilizing	0.773	D	0.367	neutral	N	0.466419206	None	None	I
T/Q	0.1884	likely_benign	0.2116	benign	-0.352	Destabilizing	0.69	D	0.368	neutral	None	None	None	None	I
T/R	0.2072	likely_benign	0.2267	benign	-0.151	Destabilizing	0.69	D	0.369	neutral	None	None	None	None	I
T/S	0.0718	likely_benign	0.0938	benign	-0.387	Destabilizing	0.001	N	0.101	neutral	N	0.35821348	None	None	I
T/V	0.1255	likely_benign	0.1691	benign	-0.23	Destabilizing	0.388	N	0.303	neutral	None	None	None	None	I
T/W	0.4811	ambiguous	0.5522	ambiguous	-0.869	Destabilizing	0.981	D	0.559	neutral	None	None	None	None	I
T/Y	0.2152	likely_benign	0.2598	benign	-0.593	Destabilizing	0.818	D	0.449	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.