TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8631	26116;26117;26118	chr2:178715523;178715522;178715521	chr2:179580250;179580249;179580248
N2AB	8314	25165;25166;25167	chr2:178715523;178715522;178715521	chr2:179580250;179580249;179580248
N2A	7387	22384;22385;22386	chr2:178715523;178715522;178715521	chr2:179580250;179580249;179580248
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-71
• Domain position: 83
• Structural Position: 166
• Q(SASA): 0.1678
• 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	rs769720173	-0.694	0.483	D	0.492	0.208	0.318828661733	gnomAD-2.1.1	2.42E-05	None	None	None	None	N	None	0	0	None	0	3.3415E-04	None	0	None	0	0	0
A/T	rs769720173	-0.694	0.483	D	0.492	0.208	0.318828661733	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	1.92753E-04	None	0	0	0	0	0
A/T	rs769720173	-0.694	0.483	D	0.492	0.208	0.318828661733	gnomAD-4.0.0	8.98124E-06	None	None	None	None	N	None	0	0	None	0	1.69779E-04	None	0	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
A/C	0.6823	likely_pathogenic	0.5829	pathogenic	-0.835	Destabilizing	0.994	D	0.52	neutral	None	None	None	None	N
A/D	0.4728	ambiguous	0.3939	ambiguous	-0.299	Destabilizing	0.004	N	0.455	neutral	N	0.509547966	None	None	N
A/E	0.5505	ambiguous	0.4814	ambiguous	-0.376	Destabilizing	0.57	D	0.514	neutral	None	None	None	None	N
A/F	0.5108	ambiguous	0.4029	ambiguous	-0.842	Destabilizing	0.98	D	0.592	neutral	None	None	None	None	N
A/G	0.2846	likely_benign	0.2213	benign	-0.795	Destabilizing	0.22	N	0.469	neutral	D	0.537313431	None	None	N
A/H	0.708	likely_pathogenic	0.63	pathogenic	-0.768	Destabilizing	0.998	D	0.552	neutral	None	None	None	None	N
A/I	0.3661	ambiguous	0.2617	benign	-0.288	Destabilizing	0.78	D	0.504	neutral	None	None	None	None	N
A/K	0.7829	likely_pathogenic	0.6991	pathogenic	-0.778	Destabilizing	0.087	N	0.372	neutral	None	None	None	None	N
A/L	0.3708	ambiguous	0.2763	benign	-0.288	Destabilizing	0.593	D	0.508	neutral	None	None	None	None	N
A/M	0.3909	ambiguous	0.2998	benign	-0.377	Destabilizing	0.98	D	0.533	neutral	None	None	None	None	N
A/N	0.4627	ambiguous	0.3714	ambiguous	-0.496	Destabilizing	0.437	N	0.585	neutral	None	None	None	None	N
A/P	0.9748	likely_pathogenic	0.9506	pathogenic	-0.355	Destabilizing	0.969	D	0.563	neutral	D	0.526210615	None	None	N
A/Q	0.5779	likely_pathogenic	0.5048	ambiguous	-0.677	Destabilizing	0.961	D	0.567	neutral	None	None	None	None	N
A/R	0.6995	likely_pathogenic	0.6229	pathogenic	-0.424	Destabilizing	0.925	D	0.567	neutral	None	None	None	None	N
A/S	0.1163	likely_benign	0.1001	benign	-0.878	Destabilizing	0.095	N	0.487	neutral	N	0.492582545	None	None	N
A/T	0.1135	likely_benign	0.0893	benign	-0.852	Destabilizing	0.483	N	0.492	neutral	D	0.532944901	None	None	N
A/V	0.1773	likely_benign	0.1298	benign	-0.355	Destabilizing	0.003	N	0.161	neutral	N	0.500600409	None	None	N
A/W	0.9103	likely_pathogenic	0.8632	pathogenic	-1.056	Destabilizing	0.998	D	0.643	neutral	None	None	None	None	N
A/Y	0.7038	likely_pathogenic	0.6082	pathogenic	-0.668	Destabilizing	0.994	D	0.584	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.