TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6168	18727;18728;18729	chr2:178729751;178729750;178729749	chr2:179594478;179594477;179594476
N2AB	5851	17776;17777;17778	chr2:178729751;178729750;178729749	chr2:179594478;179594477;179594476
N2A	4924	14995;14996;14997	chr2:178729751;178729750;178729749	chr2:179594478;179594477;179594476
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Ig-45
• Domain position: 64
• Structural Position: 144
• Q(SASA): 0.114
• 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
A/T	rs764768881	-1.37	0.006	N	0.255	0.191	0.280181792013	gnomAD-2.1.1	1.79E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	3.91E-05	0
A/T	rs764768881	-1.37	0.006	N	0.255	0.191	0.280181792013	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
A/T	rs764768881	-1.37	0.006	N	0.255	0.191	0.280181792013	gnomAD-4.0.0	2.16901E-05	None	None	None	None	N	None	1.33504E-05	0	None	0	0	None	0	0	2.88197E-05	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
A/C	0.5187	ambiguous	0.4956	ambiguous	-1.737	Destabilizing	0.973	D	0.62	neutral	None	None	None	None	N
A/D	0.5992	likely_pathogenic	0.6223	pathogenic	-1.81	Destabilizing	0.505	D	0.653	neutral	N	0.519390668	None	None	N
A/E	0.5347	ambiguous	0.5685	pathogenic	-1.801	Destabilizing	0.404	N	0.641	neutral	None	None	None	None	N
A/F	0.482	ambiguous	0.5265	ambiguous	-1.35	Destabilizing	0.906	D	0.663	neutral	None	None	None	None	N
A/G	0.1685	likely_benign	0.1883	benign	-1.471	Destabilizing	0.174	N	0.537	neutral	N	0.519137178	None	None	N
A/H	0.7543	likely_pathogenic	0.7773	pathogenic	-1.412	Destabilizing	0.973	D	0.659	neutral	None	None	None	None	N
A/I	0.2498	likely_benign	0.273	benign	-0.596	Destabilizing	0.826	D	0.681	prob.neutral	None	None	None	None	N
A/K	0.7932	likely_pathogenic	0.8132	pathogenic	-1.319	Destabilizing	0.404	N	0.638	neutral	None	None	None	None	N
A/L	0.2259	likely_benign	0.2457	benign	-0.596	Destabilizing	0.575	D	0.599	neutral	None	None	None	None	N
A/M	0.2823	likely_benign	0.3107	benign	-0.741	Destabilizing	0.991	D	0.655	neutral	None	None	None	None	N
A/N	0.4583	ambiguous	0.4878	ambiguous	-1.298	Destabilizing	0.704	D	0.669	neutral	None	None	None	None	N
A/P	0.3274	likely_benign	0.3475	ambiguous	-0.76	Destabilizing	0.879	D	0.683	prob.neutral	D	0.538758939	None	None	N
A/Q	0.6192	likely_pathogenic	0.6567	pathogenic	-1.471	Destabilizing	0.826	D	0.687	prob.neutral	None	None	None	None	N
A/R	0.7127	likely_pathogenic	0.7366	pathogenic	-0.984	Destabilizing	0.826	D	0.678	prob.neutral	None	None	None	None	N
A/S	0.1095	likely_benign	0.1176	benign	-1.724	Destabilizing	0.001	N	0.245	neutral	N	0.520018463	None	None	N
A/T	0.0978	likely_benign	0.105	benign	-1.614	Destabilizing	0.006	N	0.255	neutral	N	0.492813219	None	None	N
A/V	0.1231	likely_benign	0.1308	benign	-0.76	Destabilizing	0.505	D	0.58	neutral	N	0.446725852	None	None	N
A/W	0.8644	likely_pathogenic	0.8809	pathogenic	-1.621	Destabilizing	0.991	D	0.673	neutral	None	None	None	None	N
A/Y	0.6899	likely_pathogenic	0.7229	pathogenic	-1.216	Destabilizing	0.906	D	0.672	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.