TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24962	75109;75110;75111	chr2:178571248;178571247;178571246	chr2:179435975;179435974;179435973
N2AB	23321	70186;70187;70188	chr2:178571248;178571247;178571246	chr2:179435975;179435974;179435973
N2A	22394	67405;67406;67407	chr2:178571248;178571247;178571246	chr2:179435975;179435974;179435973
N2B	15897	47914;47915;47916	chr2:178571248;178571247;178571246	chr2:179435975;179435974;179435973
Novex-1	16022	48289;48290;48291	chr2:178571248;178571247;178571246	chr2:179435975;179435974;179435973
Novex-2	16089	48490;48491;48492	chr2:178571248;178571247;178571246	chr2:179435975;179435974;179435973
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-69
• Domain position: 55
• Structural Position: 75
• Q(SASA): 0.2934
• 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
P/S	None	None	0.891	N	0.379	0.172	0.251116650651	gnomAD-4.0.0	1.59183E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85935E-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
P/A	0.0722	likely_benign	0.0706	benign	-1.339	Destabilizing	0.625	D	0.352	neutral	D	0.52579435	None	None	N
P/C	0.3042	likely_benign	0.3228	benign	-0.639	Destabilizing	0.998	D	0.438	neutral	None	None	None	None	N
P/D	0.7382	likely_pathogenic	0.7313	pathogenic	-1.464	Destabilizing	0.991	D	0.391	neutral	None	None	None	None	N
P/E	0.4724	ambiguous	0.4579	ambiguous	-1.517	Destabilizing	0.971	D	0.386	neutral	None	None	None	None	N
P/F	0.4668	ambiguous	0.4931	ambiguous	-1.205	Destabilizing	0.949	D	0.444	neutral	None	None	None	None	N
P/G	0.3689	ambiguous	0.3919	ambiguous	-1.603	Destabilizing	0.971	D	0.361	neutral	None	None	None	None	N
P/H	0.3205	likely_benign	0.3086	benign	-1.265	Destabilizing	0.997	D	0.391	neutral	N	0.478413585	None	None	N
P/I	0.1299	likely_benign	0.1255	benign	-0.729	Destabilizing	0.007	N	0.332	neutral	None	None	None	None	N
P/K	0.4184	ambiguous	0.4093	ambiguous	-1.166	Destabilizing	0.915	D	0.349	neutral	None	None	None	None	N
P/L	0.0697	likely_benign	0.0754	benign	-0.729	Destabilizing	0.005	N	0.333	neutral	N	0.443698615	None	None	N
P/M	0.1814	likely_benign	0.1875	benign	-0.356	Destabilizing	0.949	D	0.421	neutral	None	None	None	None	N
P/N	0.4146	ambiguous	0.412	ambiguous	-0.801	Destabilizing	0.991	D	0.425	neutral	None	None	None	None	N
P/Q	0.2402	likely_benign	0.2338	benign	-1.054	Destabilizing	0.991	D	0.399	neutral	None	None	None	None	N
P/R	0.301	likely_benign	0.2857	benign	-0.565	Destabilizing	0.966	D	0.427	neutral	N	0.521369965	None	None	N
P/S	0.1668	likely_benign	0.166	benign	-1.185	Destabilizing	0.891	D	0.379	neutral	N	0.491833705	None	None	N
P/T	0.1023	likely_benign	0.1006	benign	-1.148	Destabilizing	0.801	D	0.344	neutral	N	0.473904092	None	None	N
P/V	0.0968	likely_benign	0.0936	benign	-0.898	Destabilizing	0.029	N	0.274	neutral	None	None	None	None	N
P/W	0.6603	likely_pathogenic	0.6893	pathogenic	-1.386	Destabilizing	0.998	D	0.527	neutral	None	None	None	None	N
P/Y	0.4728	ambiguous	0.4858	ambiguous	-1.129	Destabilizing	0.974	D	0.469	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.