TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19239	57940;57941;57942	chr2:178595639;178595638;178595637	chr2:179460366;179460365;179460364
N2AB	17598	53017;53018;53019	chr2:178595639;178595638;178595637	chr2:179460366;179460365;179460364
N2A	16671	50236;50237;50238	chr2:178595639;178595638;178595637	chr2:179460366;179460365;179460364
N2B	10174	30745;30746;30747	chr2:178595639;178595638;178595637	chr2:179460366;179460365;179460364
Novex-1	10299	31120;31121;31122	chr2:178595639;178595638;178595637	chr2:179460366;179460365;179460364
Novex-2	10366	31321;31322;31323	chr2:178595639;178595638;178595637	chr2:179460366;179460365;179460364
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: Fn3-27
• Domain position: 57
• Structural Position: 83
• Q(SASA): 0.7738
• 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	None	None	0.999	N	0.475	0.318	0.266843984389	gnomAD-4.0.0	6.87783E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.02426E-07	0	0
T/I	rs2051363006	None	1.0	N	0.638	0.46	0.510407551169	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	0	2.07383E-04	0
T/I	rs2051363006	None	1.0	N	0.638	0.46	0.510407551169	gnomAD-4.0.0	1.24546E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.50303E-07	1.11864E-05	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	0.1572	likely_benign	0.1803	benign	-0.607	Destabilizing	0.999	D	0.475	neutral	N	0.483062293	None	None	I
T/C	0.5889	likely_pathogenic	0.6261	pathogenic	-0.425	Destabilizing	1.0	D	0.584	neutral	None	None	None	None	I
T/D	0.7246	likely_pathogenic	0.7598	pathogenic	0.407	Stabilizing	1.0	D	0.645	neutral	None	None	None	None	I
T/E	0.6349	likely_pathogenic	0.681	pathogenic	0.363	Stabilizing	1.0	D	0.652	neutral	None	None	None	None	I
T/F	0.5452	ambiguous	0.6167	pathogenic	-0.964	Destabilizing	1.0	D	0.614	neutral	None	None	None	None	I
T/G	0.3332	likely_benign	0.3713	ambiguous	-0.779	Destabilizing	1.0	D	0.589	neutral	None	None	None	None	I
T/H	0.4842	ambiguous	0.535	ambiguous	-0.988	Destabilizing	1.0	D	0.566	neutral	None	None	None	None	I
T/I	0.4533	ambiguous	0.5196	ambiguous	-0.263	Destabilizing	1.0	D	0.638	neutral	N	0.519023093	None	None	I
T/K	0.4639	ambiguous	0.5419	ambiguous	-0.411	Destabilizing	1.0	D	0.654	neutral	None	None	None	None	I
T/L	0.1991	likely_benign	0.2307	benign	-0.263	Destabilizing	0.999	D	0.616	neutral	None	None	None	None	I
T/M	0.152	likely_benign	0.1769	benign	-0.159	Destabilizing	1.0	D	0.593	neutral	None	None	None	None	I
T/N	0.2225	likely_benign	0.2518	benign	-0.279	Destabilizing	1.0	D	0.674	neutral	N	0.496663522	None	None	I
T/P	0.1838	likely_benign	0.2088	benign	-0.348	Destabilizing	1.0	D	0.635	neutral	N	0.454702256	None	None	I
T/Q	0.3847	ambiguous	0.4231	ambiguous	-0.44	Destabilizing	1.0	D	0.653	neutral	None	None	None	None	I
T/R	0.4434	ambiguous	0.5325	ambiguous	-0.177	Destabilizing	1.0	D	0.633	neutral	None	None	None	None	I
T/S	0.1666	likely_benign	0.1855	benign	-0.572	Destabilizing	0.999	D	0.5	neutral	N	0.448640288	None	None	I
T/V	0.3237	likely_benign	0.3666	ambiguous	-0.348	Destabilizing	0.999	D	0.573	neutral	None	None	None	None	I
T/W	0.8367	likely_pathogenic	0.8711	pathogenic	-0.923	Destabilizing	1.0	D	0.597	neutral	None	None	None	None	I
T/Y	0.6162	likely_pathogenic	0.6778	pathogenic	-0.658	Destabilizing	1.0	D	0.603	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.