TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32315	97168;97169;97170	chr2:178542911;178542910;178542909	chr2:179407638;179407637;179407636
N2AB	30674	92245;92246;92247	chr2:178542911;178542910;178542909	chr2:179407638;179407637;179407636
N2A	29747	89464;89465;89466	chr2:178542911;178542910;178542909	chr2:179407638;179407637;179407636
N2B	23250	69973;69974;69975	chr2:178542911;178542910;178542909	chr2:179407638;179407637;179407636
Novex-1	23375	70348;70349;70350	chr2:178542911;178542910;178542909	chr2:179407638;179407637;179407636
Novex-2	23442	70549;70550;70551	chr2:178542911;178542910;178542909	chr2:179407638;179407637;179407636
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: Ig-154
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.4289
• 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
T/A	rs1363712214	-0.569	0.826	N	0.288	0.081	0.152612264143	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
T/A	rs1363712214	-0.569	0.826	N	0.288	0.081	0.152612264143	gnomAD-4.0.0	1.5955E-06	None	None	None	None	N	None	0	2.28822E-05	None	0	0	None	0	0	0	0	0
T/I	rs56027402	0.33	0.061	N	0.173	0.126	None	gnomAD-2.1.1	6.00651E-03	None	None	None	None	N	None	6.4336E-02	2.40698E-03	None	0	0	None	2.29223E-04	None	0	1.33894E-04	1.5493E-03
T/I	rs56027402	0.33	0.061	N	0.173	0.126	None	gnomAD-3.1.2	1.79995E-02	None	None	None	None	N	None	6.32037E-02	4.9823E-03	0	0	0	None	0	3.16456E-03	2.49934E-04	6.21375E-04	1.14833E-02
T/I	rs56027402	0.33	0.061	N	0.173	0.126	None	1000 genomes	1.63738E-02	None	None	None	None	N	None	5.75E-02	8.6E-03	None	None	0	0	None	None	None	0	None
T/I	rs56027402	0.33	0.061	N	0.173	0.126	None	gnomAD-4.0.0	3.40756E-03	None	None	None	None	N	None	6.51298E-02	3.36902E-03	None	0	0	None	0	1.81758E-03	7.46826E-05	2.1979E-04	4.64476E-03
T/N	rs56027402	None	0.996	N	0.314	0.234	0.282179105231	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.07125E-04	0
T/N	rs56027402	None	0.996	N	0.314	0.234	0.282179105231	gnomAD-4.0.0	3.72233E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	5.49451E-05	1.6022E-05
T/S	None	None	0.959	N	0.298	0.12	0.143124449307	gnomAD-4.0.0	1.5955E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02847E-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
T/A	0.1329	likely_benign	0.1215	benign	-0.803	Destabilizing	0.826	D	0.288	neutral	N	0.481797565	None	None	N
T/C	0.5063	ambiguous	0.5026	ambiguous	-0.418	Destabilizing	0.999	D	0.327	neutral	None	None	None	None	N
T/D	0.6842	likely_pathogenic	0.5656	pathogenic	-0.635	Destabilizing	0.997	D	0.331	neutral	None	None	None	None	N
T/E	0.44	ambiguous	0.3691	ambiguous	-0.569	Destabilizing	0.997	D	0.333	neutral	None	None	None	None	N
T/F	0.4041	ambiguous	0.314	benign	-0.517	Destabilizing	0.991	D	0.395	neutral	None	None	None	None	N
T/G	0.4796	ambiguous	0.4447	ambiguous	-1.141	Destabilizing	0.99	D	0.385	neutral	None	None	None	None	N
T/H	0.4274	ambiguous	0.3486	ambiguous	-1.449	Destabilizing	0.999	D	0.391	neutral	None	None	None	None	N
T/I	0.1646	likely_benign	0.1219	benign	0.035	Stabilizing	0.061	N	0.173	neutral	N	0.477295822	None	None	N
T/K	0.4268	ambiguous	0.3382	benign	-1.011	Destabilizing	0.997	D	0.325	neutral	None	None	None	None	N
T/L	0.1352	likely_benign	0.1033	benign	0.035	Stabilizing	0.579	D	0.276	neutral	None	None	None	None	N
T/M	0.0915	likely_benign	0.0808	benign	0.207	Stabilizing	0.991	D	0.321	neutral	None	None	None	None	N
T/N	0.2023	likely_benign	0.1706	benign	-1.036	Destabilizing	0.996	D	0.314	neutral	N	0.442372385	None	None	N
T/P	0.6623	likely_pathogenic	0.52	ambiguous	-0.211	Destabilizing	0.996	D	0.336	neutral	N	0.471868573	None	None	N
T/Q	0.3174	likely_benign	0.2784	benign	-1.005	Destabilizing	0.997	D	0.321	neutral	None	None	None	None	N
T/R	0.3846	ambiguous	0.2784	benign	-0.961	Destabilizing	0.997	D	0.324	neutral	None	None	None	None	N
T/S	0.192	likely_benign	0.1775	benign	-1.236	Destabilizing	0.959	D	0.298	neutral	N	0.449914433	None	None	N
T/V	0.1277	likely_benign	0.1082	benign	-0.211	Destabilizing	0.079	N	0.133	neutral	None	None	None	None	N
T/W	0.7652	likely_pathogenic	0.7014	pathogenic	-0.591	Destabilizing	0.999	D	0.447	neutral	None	None	None	None	N
T/Y	0.4089	ambiguous	0.3501	ambiguous	-0.361	Destabilizing	0.997	D	0.392	neutral	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.