TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24753	74482;74483;74484	chr2:178571875;178571874;178571873	chr2:179436602;179436601;179436600
N2AB	23112	69559;69560;69561	chr2:178571875;178571874;178571873	chr2:179436602;179436601;179436600
N2A	22185	66778;66779;66780	chr2:178571875;178571874;178571873	chr2:179436602;179436601;179436600
N2B	15688	47287;47288;47289	chr2:178571875;178571874;178571873	chr2:179436602;179436601;179436600
Novex-1	15813	47662;47663;47664	chr2:178571875;178571874;178571873	chr2:179436602;179436601;179436600
Novex-2	15880	47863;47864;47865	chr2:178571875;178571874;178571873	chr2:179436602;179436601;179436600
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-133
• Domain position: 38
• Structural Position: 52
• Q(SASA): 0.8223
• 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
N/K	None	None	0.029	N	0.191	0.088	0.0138822411134	gnomAD-4.0.0	6.84323E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.9959E-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
N/A	0.1327	likely_benign	0.1212	benign	-0.247	Destabilizing	None	N	0.213	neutral	None	None	None	None	I
N/C	0.2292	likely_benign	0.2103	benign	0.409	Stabilizing	0.676	D	0.333	neutral	None	None	None	None	I
N/D	0.0692	likely_benign	0.0636	benign	0.108	Stabilizing	None	N	0.155	neutral	N	0.435870487	None	None	I
N/E	0.1578	likely_benign	0.1546	benign	0.081	Stabilizing	None	N	0.151	neutral	None	None	None	None	I
N/F	0.4484	ambiguous	0.4079	ambiguous	-0.601	Destabilizing	0.356	N	0.342	neutral	None	None	None	None	I
N/G	0.1206	likely_benign	0.1097	benign	-0.425	Destabilizing	None	N	0.121	neutral	None	None	None	None	I
N/H	0.1052	likely_benign	0.1034	benign	-0.484	Destabilizing	0.295	N	0.265	neutral	N	0.505810575	None	None	I
N/I	0.2269	likely_benign	0.2114	benign	0.138	Stabilizing	0.171	N	0.391	neutral	N	0.453681106	None	None	I
N/K	0.1736	likely_benign	0.17	benign	0.023	Stabilizing	0.029	N	0.191	neutral	N	0.487992818	None	None	I
N/L	0.2253	likely_benign	0.2143	benign	0.138	Stabilizing	0.038	N	0.427	neutral	None	None	None	None	I
N/M	0.265	likely_benign	0.2551	benign	0.332	Stabilizing	0.864	D	0.315	neutral	None	None	None	None	I
N/P	0.626	likely_pathogenic	0.5984	pathogenic	0.036	Stabilizing	0.136	N	0.399	neutral	None	None	None	None	I
N/Q	0.1851	likely_benign	0.1811	benign	-0.221	Destabilizing	0.038	N	0.252	neutral	None	None	None	None	I
N/R	0.2128	likely_benign	0.2013	benign	0.036	Stabilizing	0.072	N	0.247	neutral	None	None	None	None	I
N/S	0.0727	likely_benign	0.0704	benign	-0.046	Destabilizing	0.012	N	0.286	neutral	N	0.450647939	None	None	I
N/T	0.1079	likely_benign	0.1057	benign	0.06	Stabilizing	0.055	N	0.192	neutral	N	0.494073429	None	None	I
N/V	0.2026	likely_benign	0.1887	benign	0.036	Stabilizing	0.038	N	0.429	neutral	None	None	None	None	I
N/W	0.6854	likely_pathogenic	0.6464	pathogenic	-0.647	Destabilizing	0.864	D	0.378	neutral	None	None	None	None	I
N/Y	0.177	likely_benign	0.1599	benign	-0.375	Destabilizing	0.56	D	0.319	neutral	N	0.458200556	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.