TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23589	70990;70991;70992	chr2:178575367;178575366;178575365	chr2:179440094;179440093;179440092
N2AB	21948	66067;66068;66069	chr2:178575367;178575366;178575365	chr2:179440094;179440093;179440092
N2A	21021	63286;63287;63288	chr2:178575367;178575366;178575365	chr2:179440094;179440093;179440092
N2B	14524	43795;43796;43797	chr2:178575367;178575366;178575365	chr2:179440094;179440093;179440092
Novex-1	14649	44170;44171;44172	chr2:178575367;178575366;178575365	chr2:179440094;179440093;179440092
Novex-2	14716	44371;44372;44373	chr2:178575367;178575366;178575365	chr2:179440094;179440093;179440092
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-59
• Domain position: 58
• Structural Position: 90
• Q(SASA): 0.6123
• 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
E/K	None	None	0.88	N	0.533	0.332	0.254761474806	gnomAD-4.0.0	1.59176E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85899E-06	0	0
E/Q	rs776167958	-0.666	0.914	N	0.588	0.247	0.286848849266	gnomAD-2.1.1	8.05E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
E/Q	rs776167958	-0.666	0.914	N	0.588	0.247	0.286848849266	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/Q	rs776167958	-0.666	0.914	N	0.588	0.247	0.286848849266	gnomAD-4.0.0	6.57177E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.4705E-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
E/A	0.2369	likely_benign	0.2129	benign	-0.485	Destabilizing	0.799	D	0.565	neutral	N	0.515555927	None	None	I
E/C	0.8759	likely_pathogenic	0.8702	pathogenic	-0.358	Destabilizing	0.998	D	0.731	prob.delet.	None	None	None	None	I
E/D	0.1065	likely_benign	0.1168	benign	-0.52	Destabilizing	None	N	0.259	neutral	N	0.501242622	None	None	I
E/F	0.8225	likely_pathogenic	0.8107	pathogenic	0.126	Stabilizing	0.995	D	0.716	prob.delet.	None	None	None	None	I
E/G	0.2784	likely_benign	0.2582	benign	-0.769	Destabilizing	0.93	D	0.572	neutral	N	0.475256352	None	None	I
E/H	0.5094	ambiguous	0.49	ambiguous	0.418	Stabilizing	0.993	D	0.638	neutral	None	None	None	None	I
E/I	0.5731	likely_pathogenic	0.5331	ambiguous	0.264	Stabilizing	0.97	D	0.717	prob.delet.	None	None	None	None	I
E/K	0.4023	ambiguous	0.3581	ambiguous	0.138	Stabilizing	0.88	D	0.533	neutral	N	0.491660347	None	None	I
E/L	0.5969	likely_pathogenic	0.56	ambiguous	0.264	Stabilizing	0.97	D	0.677	prob.neutral	None	None	None	None	I
E/M	0.6655	likely_pathogenic	0.6237	pathogenic	0.263	Stabilizing	0.985	D	0.699	prob.neutral	None	None	None	None	I
E/N	0.2844	likely_benign	0.2862	benign	-0.525	Destabilizing	0.515	D	0.541	neutral	None	None	None	None	I
E/P	0.9123	likely_pathogenic	0.8986	pathogenic	0.035	Stabilizing	0.829	D	0.661	neutral	None	None	None	None	I
E/Q	0.2042	likely_benign	0.1807	benign	-0.409	Destabilizing	0.914	D	0.588	neutral	N	0.501010549	None	None	I
E/R	0.4935	ambiguous	0.4535	ambiguous	0.552	Stabilizing	0.986	D	0.613	neutral	None	None	None	None	I
E/S	0.2192	likely_benign	0.208	benign	-0.704	Destabilizing	0.84	D	0.52	neutral	None	None	None	None	I
E/T	0.2848	likely_benign	0.2548	benign	-0.452	Destabilizing	0.937	D	0.618	neutral	None	None	None	None	I
E/V	0.3495	ambiguous	0.3198	benign	0.035	Stabilizing	0.946	D	0.634	neutral	N	0.515075924	None	None	I
E/W	0.9306	likely_pathogenic	0.9256	pathogenic	0.424	Stabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	I
E/Y	0.6832	likely_pathogenic	0.6777	pathogenic	0.412	Stabilizing	0.998	D	0.71	prob.delet.	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.