TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21126	63601;63602;63603	chr2:178588031;178588030;178588029	chr2:179452758;179452757;179452756
N2AB	19485	58678;58679;58680	chr2:178588031;178588030;178588029	chr2:179452758;179452757;179452756
N2A	18558	55897;55898;55899	chr2:178588031;178588030;178588029	chr2:179452758;179452757;179452756
N2B	12061	36406;36407;36408	chr2:178588031;178588030;178588029	chr2:179452758;179452757;179452756
Novex-1	12186	36781;36782;36783	chr2:178588031;178588030;178588029	chr2:179452758;179452757;179452756
Novex-2	12253	36982;36983;36984	chr2:178588031;178588030;178588029	chr2:179452758;179452757;179452756
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: Fn3-41
• Domain position: 63
• Structural Position: 83
• Q(SASA): 0.5716
• 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/I	rs2049411703	None	None	N	0.167	0.037	0.295623431141	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
V/I	rs2049411703	None	None	N	0.167	0.037	0.295623431141	gnomAD-4.0.0	2.03014E-06	None	None	None	None	I	None	1.74727E-05	0	None	0	0	None	0	0	1.20501E-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	0.2464	likely_benign	0.2311	benign	-0.998	Destabilizing	0.104	N	0.402	neutral	N	0.459899353	None	None	I
V/C	0.6628	likely_pathogenic	0.6587	pathogenic	-0.795	Destabilizing	0.968	D	0.548	neutral	None	None	None	None	I
V/D	0.4531	ambiguous	0.4426	ambiguous	-0.756	Destabilizing	0.726	D	0.633	neutral	None	None	None	None	I
V/E	0.3629	ambiguous	0.3314	benign	-0.764	Destabilizing	0.667	D	0.591	neutral	N	0.473020579	None	None	I
V/F	0.1707	likely_benign	0.1807	benign	-0.702	Destabilizing	0.567	D	0.549	neutral	None	None	None	None	I
V/G	0.2332	likely_benign	0.2137	benign	-1.263	Destabilizing	0.667	D	0.633	neutral	N	0.484776368	None	None	I
V/H	0.5256	ambiguous	0.5165	ambiguous	-0.578	Destabilizing	0.968	D	0.65	neutral	None	None	None	None	I
V/I	0.0716	likely_benign	0.0804	benign	-0.39	Destabilizing	None	N	0.167	neutral	N	0.435350412	None	None	I
V/K	0.3884	ambiguous	0.3517	ambiguous	-0.899	Destabilizing	0.726	D	0.595	neutral	None	None	None	None	I
V/L	0.1466	likely_benign	0.1543	benign	-0.39	Destabilizing	0.009	N	0.296	neutral	N	0.46688404	None	None	I
V/M	0.176	likely_benign	0.1835	benign	-0.486	Destabilizing	0.567	D	0.487	neutral	None	None	None	None	I
V/N	0.2799	likely_benign	0.2736	benign	-0.801	Destabilizing	0.89	D	0.633	neutral	None	None	None	None	I
V/P	0.306	likely_benign	0.2709	benign	-0.558	Destabilizing	0.89	D	0.581	neutral	None	None	None	None	I
V/Q	0.3064	likely_benign	0.2731	benign	-0.942	Destabilizing	0.89	D	0.594	neutral	None	None	None	None	I
V/R	0.3224	likely_benign	0.287	benign	-0.366	Destabilizing	0.726	D	0.63	neutral	None	None	None	None	I
V/S	0.2516	likely_benign	0.2312	benign	-1.263	Destabilizing	0.726	D	0.524	neutral	None	None	None	None	I
V/T	0.2372	likely_benign	0.2235	benign	-1.159	Destabilizing	0.272	N	0.429	neutral	None	None	None	None	I
V/W	0.7165	likely_pathogenic	0.7268	pathogenic	-0.854	Destabilizing	0.968	D	0.694	prob.neutral	None	None	None	None	I
V/Y	0.5005	ambiguous	0.4928	ambiguous	-0.559	Destabilizing	0.726	D	0.538	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.