TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22536	67831;67832;67833	chr2:178579591;178579590;178579589	chr2:179444318;179444317;179444316
N2AB	20895	62908;62909;62910	chr2:178579591;178579590;178579589	chr2:179444318;179444317;179444316
N2A	19968	60127;60128;60129	chr2:178579591;178579590;178579589	chr2:179444318;179444317;179444316
N2B	13471	40636;40637;40638	chr2:178579591;178579590;178579589	chr2:179444318;179444317;179444316
Novex-1	13596	41011;41012;41013	chr2:178579591;178579590;178579589	chr2:179444318;179444317;179444316
Novex-2	13663	41212;41213;41214	chr2:178579591;178579590;178579589	chr2:179444318;179444317;179444316
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: Fn3-51
• Domain position: 86
• Structural Position: 122
• Q(SASA): 0.4002
• 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
E/K	rs371105318	0.044	1.0	N	0.8	0.315	None	gnomAD-2.1.1	2.15E-05	None	None	None	None	N	None	0	0	None	0	5.14E-05	None	0	None	0	3.93E-05	0
E/K	rs371105318	0.044	1.0	N	0.8	0.315	None	gnomAD-3.1.2	5.92E-05	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	1.17699E-04	0	0
E/K	rs371105318	0.044	1.0	N	0.8	0.315	None	gnomAD-4.0.0	3.78144E-05	None	None	None	None	N	None	1.33529E-05	0	None	0	4.46229E-05	None	0	0	4.83262E-05	0	1.60164E-05

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	0.2432	likely_benign	0.2415	benign	-0.78	Destabilizing	0.997	D	0.804	deleterious	N	0.504818858	None	None	N
E/C	0.8886	likely_pathogenic	0.8734	pathogenic	-0.413	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
E/D	0.2559	likely_benign	0.2652	benign	-0.875	Destabilizing	0.997	D	0.739	deleterious	N	0.4777469	None	None	N
E/F	0.7912	likely_pathogenic	0.8118	pathogenic	-0.015	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
E/G	0.307	likely_benign	0.3276	benign	-1.142	Destabilizing	0.999	D	0.735	deleterious	N	0.468037422	None	None	N
E/H	0.5467	ambiguous	0.5645	pathogenic	-0.064	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
E/I	0.3932	ambiguous	0.4164	ambiguous	0.209	Stabilizing	0.999	D	0.807	deleterious	None	None	None	None	N
E/K	0.1922	likely_benign	0.2271	benign	-0.289	Destabilizing	1.0	D	0.8	deleterious	N	0.521153748	None	None	N
E/L	0.4832	ambiguous	0.4972	ambiguous	0.209	Stabilizing	0.999	D	0.743	deleterious	None	None	None	None	N
E/M	0.4773	ambiguous	0.4935	ambiguous	0.513	Stabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
E/N	0.3817	ambiguous	0.3987	ambiguous	-0.949	Destabilizing	0.999	D	0.794	deleterious	None	None	None	None	N
E/P	0.83	likely_pathogenic	0.8216	pathogenic	-0.099	Destabilizing	0.999	D	0.778	deleterious	None	None	None	None	N
E/Q	0.1606	likely_benign	0.1659	benign	-0.795	Destabilizing	1.0	D	0.797	deleterious	N	0.513168983	None	None	N
E/R	0.3242	likely_benign	0.3694	ambiguous	0.082	Stabilizing	0.999	D	0.791	deleterious	None	None	None	None	N
E/S	0.281	likely_benign	0.2793	benign	-1.211	Destabilizing	0.998	D	0.809	deleterious	None	None	None	None	N
E/T	0.2463	likely_benign	0.2475	benign	-0.896	Destabilizing	0.999	D	0.77	deleterious	None	None	None	None	N
E/V	0.2333	likely_benign	0.2388	benign	-0.099	Destabilizing	0.999	D	0.773	deleterious	D	0.523810051	None	None	N
E/W	0.9316	likely_pathogenic	0.9424	pathogenic	0.334	Stabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
E/Y	0.7073	likely_pathogenic	0.7418	pathogenic	0.278	Stabilizing	1.0	D	0.837	deleterious	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.