TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23349	70270;70271;70272	chr2:178576087;178576086;178576085	chr2:179440814;179440813;179440812
N2AB	21708	65347;65348;65349	chr2:178576087;178576086;178576085	chr2:179440814;179440813;179440812
N2A	20781	62566;62567;62568	chr2:178576087;178576086;178576085	chr2:179440814;179440813;179440812
N2B	14284	43075;43076;43077	chr2:178576087;178576086;178576085	chr2:179440814;179440813;179440812
Novex-1	14409	43450;43451;43452	chr2:178576087;178576086;178576085	chr2:179440814;179440813;179440812
Novex-2	14476	43651;43652;43653	chr2:178576087;178576086;178576085	chr2:179440814;179440813;179440812
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: Ig-129
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.665
• 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/D	rs774136558	-0.159	0.025	N	0.363	0.064	0.21737058555	gnomAD-2.1.1	3.57E-05	None	None	None	None	I	None	0	0	None	0	5.1435E-04	None	0	None	0	0	0
E/D	rs774136558	-0.159	0.025	N	0.363	0.064	0.21737058555	gnomAD-3.1.2	1.32E-05	None	None	None	None	I	None	0	0	0	0	3.87297E-04	None	0	0	0	0	0
E/D	rs774136558	-0.159	0.025	N	0.363	0.064	0.21737058555	gnomAD-4.0.0	5.57836E-06	None	None	None	None	I	None	0	0	None	0	2.00857E-04	None	0	0	0	0	0
E/K	rs397517682	0.673	0.979	N	0.536	0.313	None	gnomAD-2.1.1	1.07E-05	None	None	None	None	I	None	0	0	None	0	5.15E-05	None	3.27E-05	None	0	7.82E-06	0
E/K	rs397517682	0.673	0.979	N	0.536	0.313	None	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	1.93723E-04	None	0	0	0	0	0
E/K	rs397517682	0.673	0.979	N	0.536	0.313	None	gnomAD-4.0.0	4.95879E-06	None	None	None	None	I	None	0	0	None	0	2.23204E-05	None	0	0	1.6955E-06	4.3929E-05	1.60149E-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	0.4967	ambiguous	0.4513	ambiguous	-0.355	Destabilizing	0.892	D	0.5	neutral	N	0.450534161	None	None	I
E/C	0.979	likely_pathogenic	0.9744	pathogenic	-0.128	Destabilizing	0.999	D	0.659	neutral	None	None	None	None	I
E/D	0.1936	likely_benign	0.1508	benign	-0.316	Destabilizing	0.025	N	0.363	neutral	N	0.409303614	None	None	I
E/F	0.9715	likely_pathogenic	0.9658	pathogenic	-0.136	Destabilizing	0.999	D	0.625	neutral	None	None	None	None	I
E/G	0.5428	ambiguous	0.5015	ambiguous	-0.571	Destabilizing	0.805	D	0.507	neutral	N	0.493575649	None	None	I
E/H	0.8855	likely_pathogenic	0.8566	pathogenic	0.096	Stabilizing	0.987	D	0.486	neutral	None	None	None	None	I
E/I	0.8877	likely_pathogenic	0.8554	pathogenic	0.185	Stabilizing	0.987	D	0.641	neutral	None	None	None	None	I
E/K	0.7337	likely_pathogenic	0.6715	pathogenic	0.233	Stabilizing	0.979	D	0.536	neutral	N	0.449342083	None	None	I
E/L	0.8786	likely_pathogenic	0.8445	pathogenic	0.185	Stabilizing	0.987	D	0.624	neutral	None	None	None	None	I
E/M	0.8943	likely_pathogenic	0.8747	pathogenic	0.215	Stabilizing	0.999	D	0.567	neutral	None	None	None	None	I
E/N	0.5879	likely_pathogenic	0.5278	ambiguous	-0.125	Destabilizing	0.073	N	0.369	neutral	None	None	None	None	I
E/P	0.9152	likely_pathogenic	0.8946	pathogenic	0.026	Stabilizing	0.996	D	0.495	neutral	None	None	None	None	I
E/Q	0.518	ambiguous	0.4687	ambiguous	-0.06	Destabilizing	0.987	D	0.459	neutral	N	0.485417526	None	None	I
E/R	0.8195	likely_pathogenic	0.7789	pathogenic	0.481	Stabilizing	0.975	D	0.481	neutral	None	None	None	None	I
E/S	0.4762	ambiguous	0.4322	ambiguous	-0.293	Destabilizing	0.845	D	0.52	neutral	None	None	None	None	I
E/T	0.6623	likely_pathogenic	0.5989	pathogenic	-0.114	Destabilizing	0.916	D	0.457	neutral	None	None	None	None	I
E/V	0.7251	likely_pathogenic	0.6675	pathogenic	0.026	Stabilizing	0.983	D	0.565	neutral	D	0.52355184	None	None	I
E/W	0.9913	likely_pathogenic	0.9891	pathogenic	0.027	Stabilizing	0.999	D	0.659	neutral	None	None	None	None	I
E/Y	0.9388	likely_pathogenic	0.9198	pathogenic	0.104	Stabilizing	0.996	D	0.566	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.