TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23170	69733;69734;69735	chr2:178576736;178576735;178576734	chr2:179441463;179441462;179441461
N2AB	21529	64810;64811;64812	chr2:178576736;178576735;178576734	chr2:179441463;179441462;179441461
N2A	20602	62029;62030;62031	chr2:178576736;178576735;178576734	chr2:179441463;179441462;179441461
N2B	14105	42538;42539;42540	chr2:178576736;178576735;178576734	chr2:179441463;179441462;179441461
Novex-1	14230	42913;42914;42915	chr2:178576736;178576735;178576734	chr2:179441463;179441462;179441461
Novex-2	14297	43114;43115;43116	chr2:178576736;178576735;178576734	chr2:179441463;179441462;179441461
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: Fn3-56
• Domain position: 32
• Structural Position: 34
• Q(SASA): 0.3588
• 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	rs760127657	-0.375	0.006	N	0.051	0.01	0.163833314356	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/D	rs760127657	-0.375	0.006	N	0.051	0.01	0.163833314356	gnomAD-4.0.0	1.09485E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.4393E-05	0	0
E/K	rs1334543067	0.365	0.963	N	0.429	0.274	0.3085936734	gnomAD-2.1.1	1.43E-05	None	None	None	None	I	None	0	2.83E-05	None	0	0	None	3.27E-05	None	0	1.57E-05	0
E/K	rs1334543067	0.365	0.963	N	0.429	0.274	0.3085936734	gnomAD-3.1.2	1.32E-05	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	1.47E-05	0	0
E/K	rs1334543067	0.365	0.963	N	0.429	0.274	0.3085936734	gnomAD-4.0.0	1.15348E-05	None	None	None	None	I	None	1.69256E-05	1.69497E-05	None	0	0	None	0	2.24316E-04	7.18205E-06	1.34034E-05	5.69022E-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	0.1906	likely_benign	0.186	benign	-0.392	Destabilizing	0.822	D	0.442	neutral	N	0.482907578	None	None	I
E/C	0.8722	likely_pathogenic	0.8685	pathogenic	0.072	Stabilizing	0.998	D	0.667	neutral	None	None	None	None	I
E/D	0.0953	likely_benign	0.0916	benign	-0.309	Destabilizing	0.006	N	0.051	neutral	N	0.450872517	None	None	I
E/F	0.8275	likely_pathogenic	0.8301	pathogenic	-0.327	Destabilizing	0.993	D	0.609	neutral	None	None	None	None	I
E/G	0.2676	likely_benign	0.2578	benign	-0.587	Destabilizing	0.822	D	0.513	neutral	N	0.521484608	None	None	I
E/H	0.568	likely_pathogenic	0.5712	pathogenic	-0.193	Destabilizing	0.993	D	0.426	neutral	None	None	None	None	I
E/I	0.4321	ambiguous	0.4361	ambiguous	0.088	Stabilizing	0.978	D	0.619	neutral	None	None	None	None	I
E/K	0.2609	likely_benign	0.2869	benign	0.382	Stabilizing	0.963	D	0.429	neutral	N	0.481310067	None	None	I
E/L	0.4799	ambiguous	0.4785	ambiguous	0.088	Stabilizing	0.956	D	0.537	neutral	None	None	None	None	I
E/M	0.5563	ambiguous	0.5383	ambiguous	0.271	Stabilizing	0.998	D	0.583	neutral	None	None	None	None	I
E/N	0.2873	likely_benign	0.2735	benign	0.083	Stabilizing	0.86	D	0.418	neutral	None	None	None	None	I
E/P	0.319	likely_benign	0.2749	benign	-0.052	Destabilizing	0.019	N	0.25	neutral	None	None	None	None	I
E/Q	0.1974	likely_benign	0.2006	benign	0.116	Stabilizing	0.96	D	0.424	neutral	N	0.482542218	None	None	I
E/R	0.3816	ambiguous	0.3934	ambiguous	0.507	Stabilizing	0.978	D	0.44	neutral	None	None	None	None	I
E/S	0.2396	likely_benign	0.2323	benign	-0.076	Destabilizing	0.86	D	0.404	neutral	None	None	None	None	I
E/T	0.298	likely_benign	0.2944	benign	0.086	Stabilizing	0.86	D	0.501	neutral	None	None	None	None	I
E/V	0.26	likely_benign	0.2617	benign	-0.052	Destabilizing	0.97	D	0.497	neutral	N	0.480651629	None	None	I
E/W	0.9365	likely_pathogenic	0.9361	pathogenic	-0.188	Destabilizing	0.998	D	0.703	prob.neutral	None	None	None	None	I
E/Y	0.7077	likely_pathogenic	0.717	pathogenic	-0.084	Destabilizing	0.993	D	0.587	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.