TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28504	85735;85736;85737	chr2:178560622;178560621;178560620	chr2:179425349;179425348;179425347
N2AB	26863	80812;80813;80814	chr2:178560622;178560621;178560620	chr2:179425349;179425348;179425347
N2A	25936	78031;78032;78033	chr2:178560622;178560621;178560620	chr2:179425349;179425348;179425347
N2B	19439	58540;58541;58542	chr2:178560622;178560621;178560620	chr2:179425349;179425348;179425347
Novex-1	19564	58915;58916;58917	chr2:178560622;178560621;178560620	chr2:179425349;179425348;179425347
Novex-2	19631	59116;59117;59118	chr2:178560622;178560621;178560620	chr2:179425349;179425348;179425347
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-95
• Domain position: 55
• Structural Position: 75
• Q(SASA): 0.7784
• 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	rs876657670	None	0.379	N	0.433	0.179	0.295623431141	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/K	rs876657670	None	0.379	N	0.433	0.179	0.295623431141	gnomAD-4.0.0	6.57229E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.46994E-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	0.1449	likely_benign	0.1416	benign	-0.479	Destabilizing	0.379	N	0.455	neutral	N	0.473631946	None	None	I
E/C	0.7046	likely_pathogenic	0.7122	pathogenic	-0.39	Destabilizing	0.992	D	0.563	neutral	None	None	None	None	I
E/D	0.1318	likely_benign	0.1434	benign	-0.41	Destabilizing	0.001	N	0.138	neutral	N	0.423568486	None	None	I
E/F	0.5895	likely_pathogenic	0.6025	pathogenic	-0.022	Destabilizing	0.972	D	0.485	neutral	None	None	None	None	I
E/G	0.1477	likely_benign	0.1302	benign	-0.722	Destabilizing	0.549	D	0.457	neutral	N	0.463569668	None	None	I
E/H	0.3197	likely_benign	0.3175	benign	0.33	Stabilizing	0.92	D	0.425	neutral	None	None	None	None	I
E/I	0.2995	likely_benign	0.3057	benign	0.148	Stabilizing	0.92	D	0.483	neutral	None	None	None	None	I
E/K	0.098	likely_benign	0.0927	benign	0.114	Stabilizing	0.379	N	0.433	neutral	N	0.439634016	None	None	I
E/L	0.3409	ambiguous	0.3384	benign	0.148	Stabilizing	0.85	D	0.424	neutral	None	None	None	None	I
E/M	0.3678	ambiguous	0.3689	ambiguous	0.097	Stabilizing	0.977	D	0.472	neutral	None	None	None	None	I
E/N	0.1806	likely_benign	0.1862	benign	-0.427	Destabilizing	0.617	D	0.427	neutral	None	None	None	None	I
E/P	0.3644	ambiguous	0.391	ambiguous	-0.041	Destabilizing	0.92	D	0.433	neutral	None	None	None	None	I
E/Q	0.106	likely_benign	0.1039	benign	-0.338	Destabilizing	0.016	N	0.219	neutral	N	0.500357188	None	None	I
E/R	0.1576	likely_benign	0.1501	benign	0.506	Stabilizing	0.739	D	0.393	neutral	None	None	None	None	I
E/S	0.1692	likely_benign	0.1691	benign	-0.599	Destabilizing	0.447	N	0.409	neutral	None	None	None	None	I
E/T	0.2035	likely_benign	0.2038	benign	-0.387	Destabilizing	0.617	D	0.451	neutral	None	None	None	None	I
E/V	0.1949	likely_benign	0.1971	benign	-0.041	Destabilizing	0.81	D	0.42	neutral	N	0.482155429	None	None	I
E/W	0.8021	likely_pathogenic	0.8037	pathogenic	0.229	Stabilizing	0.992	D	0.641	neutral	None	None	None	None	I
E/Y	0.44	ambiguous	0.452	ambiguous	0.24	Stabilizing	0.92	D	0.471	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.