TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31221	93886;93887;93888	chr2:178547965;178547964;178547963	chr2:179412692;179412691;179412690
N2AB	29580	88963;88964;88965	chr2:178547965;178547964;178547963	chr2:179412692;179412691;179412690
N2A	28653	86182;86183;86184	chr2:178547965;178547964;178547963	chr2:179412692;179412691;179412690
N2B	22156	66691;66692;66693	chr2:178547965;178547964;178547963	chr2:179412692;179412691;179412690
Novex-1	22281	67066;67067;67068	chr2:178547965;178547964;178547963	chr2:179412692;179412691;179412690
Novex-2	22348	67267;67268;67269	chr2:178547965;178547964;178547963	chr2:179412692;179412691;179412690
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-151
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.3598
• 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
T/N	None	None	0.939	N	0.579	0.208	0.434716162284	gnomAD-4.0.0	2.05282E-06	None	None	None	None	N	None	0	2.23754E-05	None	0	0	None	0	0	1.79903E-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
T/A	0.0843	likely_benign	0.0805	benign	-0.19	Destabilizing	0.76	D	0.558	neutral	N	0.474024309	None	None	N
T/C	0.4677	ambiguous	0.4107	ambiguous	-0.356	Destabilizing	0.999	D	0.643	neutral	None	None	None	None	N
T/D	0.4282	ambiguous	0.376	ambiguous	0.155	Stabilizing	0.06	N	0.408	neutral	None	None	None	None	N
T/E	0.3281	likely_benign	0.2933	benign	0.068	Stabilizing	0.91	D	0.581	neutral	None	None	None	None	N
T/F	0.3911	ambiguous	0.351	ambiguous	-0.819	Destabilizing	0.998	D	0.668	neutral	None	None	None	None	N
T/G	0.2132	likely_benign	0.1887	benign	-0.268	Destabilizing	0.91	D	0.567	neutral	None	None	None	None	N
T/H	0.2623	likely_benign	0.2278	benign	-0.516	Destabilizing	0.999	D	0.663	neutral	None	None	None	None	N
T/I	0.2707	likely_benign	0.2573	benign	-0.11	Destabilizing	0.991	D	0.676	prob.neutral	N	0.445781702	None	None	N
T/K	0.2042	likely_benign	0.1774	benign	-0.29	Destabilizing	0.986	D	0.642	neutral	None	None	None	None	N
T/L	0.1512	likely_benign	0.1524	benign	-0.11	Destabilizing	0.953	D	0.606	neutral	None	None	None	None	N
T/M	0.1353	likely_benign	0.1352	benign	-0.113	Destabilizing	0.999	D	0.651	neutral	None	None	None	None	N
T/N	0.1382	likely_benign	0.1231	benign	-0.139	Destabilizing	0.939	D	0.579	neutral	N	0.493572862	None	None	N
T/P	0.0751	likely_benign	0.079	benign	-0.111	Destabilizing	0.991	D	0.668	neutral	N	0.445088269	None	None	N
T/Q	0.2053	likely_benign	0.1899	benign	-0.327	Destabilizing	0.993	D	0.677	prob.neutral	None	None	None	None	N
T/R	0.1822	likely_benign	0.1632	benign	-0.053	Destabilizing	0.986	D	0.679	prob.neutral	None	None	None	None	N
T/S	0.104	likely_benign	0.0894	benign	-0.298	Destabilizing	0.17	N	0.417	neutral	N	0.474197668	None	None	N
T/V	0.197	likely_benign	0.1872	benign	-0.111	Destabilizing	0.953	D	0.585	neutral	None	None	None	None	N
T/W	0.6153	likely_pathogenic	0.5822	pathogenic	-0.897	Destabilizing	0.999	D	0.652	neutral	None	None	None	None	N
T/Y	0.3457	ambiguous	0.303	benign	-0.575	Destabilizing	0.998	D	0.667	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.