TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1086	3481;3482;3483	chr2:178782336;178782335;178782334	chr2:179647063;179647062;179647061
N2AB	1086	3481;3482;3483	chr2:178782336;178782335;178782334	chr2:179647063;179647062;179647061
N2A	1086	3481;3482;3483	chr2:178782336;178782335;178782334	chr2:179647063;179647062;179647061
N2B	1040	3343;3344;3345	chr2:178782336;178782335;178782334	chr2:179647063;179647062;179647061
Novex-1	1040	3343;3344;3345	chr2:178782336;178782335;178782334	chr2:179647063;179647062;179647061
Novex-2	1040	3343;3344;3345	chr2:178782336;178782335;178782334	chr2:179647063;179647062;179647061
Novex-3	1086	3481;3482;3483	chr2:178782336;178782335;178782334	chr2:179647063;179647062;179647061

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-4
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.2784
• 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/A	rs1167240676	-0.786	0.005	N	0.189	0.063	0.185906805712	gnomAD-2.1.1	3.98E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.81E-06	0
T/A	rs1167240676	-0.786	0.005	N	0.189	0.063	0.185906805712	gnomAD-4.0.0	1.59056E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85657E-06	0	0
T/R	None	None	None	N	0.103	0.096	0.439339381091	gnomAD-4.0.0	1.59054E-06	None	None	None	None	I	None	0	0	None	0	0	None	1.88196E-05	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	0.0972	likely_benign	0.1004	benign	-0.672	Destabilizing	0.005	N	0.189	neutral	N	0.503232621	None	None	I
T/C	0.5233	ambiguous	0.5106	ambiguous	-0.419	Destabilizing	0.356	N	0.317	neutral	None	None	None	None	I
T/D	0.4461	ambiguous	0.4576	ambiguous	0.057	Stabilizing	0.016	N	0.333	neutral	None	None	None	None	I
T/E	0.271	likely_benign	0.2903	benign	0.058	Stabilizing	0.007	N	0.298	neutral	None	None	None	None	I
T/F	0.3237	likely_benign	0.3278	benign	-0.748	Destabilizing	0.214	N	0.463	neutral	None	None	None	None	I
T/G	0.2693	likely_benign	0.2546	benign	-0.926	Destabilizing	0.016	N	0.28	neutral	None	None	None	None	I
T/H	0.2673	likely_benign	0.2778	benign	-1.126	Destabilizing	0.356	N	0.41	neutral	None	None	None	None	I
T/I	0.2352	likely_benign	0.2578	benign	-0.092	Destabilizing	0.029	N	0.349	neutral	N	0.489513398	None	None	I
T/K	0.1806	likely_benign	0.2061	benign	-0.635	Destabilizing	None	N	0.091	neutral	N	0.464376799	None	None	I
T/L	0.1353	likely_benign	0.1348	benign	-0.092	Destabilizing	0.002	N	0.305	neutral	None	None	None	None	I
T/M	0.1185	likely_benign	0.1233	benign	0.021	Stabilizing	0.001	N	0.199	neutral	None	None	None	None	I
T/N	0.1617	likely_benign	0.1692	benign	-0.565	Destabilizing	0.016	N	0.188	neutral	None	None	None	None	I
T/P	0.4612	ambiguous	0.4865	ambiguous	-0.253	Destabilizing	0.055	N	0.357	neutral	N	0.516655465	None	None	I
T/Q	0.1756	likely_benign	0.192	benign	-0.667	Destabilizing	0.001	N	0.113	neutral	None	None	None	None	I
T/R	0.1298	likely_benign	0.1506	benign	-0.419	Destabilizing	None	N	0.103	neutral	N	0.475691818	None	None	I
T/S	0.1003	likely_benign	0.1005	benign	-0.846	Destabilizing	None	N	0.099	neutral	N	0.49114849	None	None	I
T/V	0.1691	likely_benign	0.1786	benign	-0.253	Destabilizing	0.016	N	0.206	neutral	None	None	None	None	I
T/W	0.6345	likely_pathogenic	0.6416	pathogenic	-0.726	Destabilizing	0.864	D	0.375	neutral	None	None	None	None	I
T/Y	0.3622	ambiguous	0.3754	ambiguous	-0.481	Destabilizing	0.356	N	0.479	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.