TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15272	46039;46040;46041	chr2:178620796;178620795;178620794	chr2:179485523;179485522;179485521
N2AB	13631	41116;41117;41118	chr2:178620796;178620795;178620794	chr2:179485523;179485522;179485521
N2A	12704	38335;38336;38337	chr2:178620796;178620795;178620794	chr2:179485523;179485522;179485521
N2B	6207	18844;18845;18846	chr2:178620796;178620795;178620794	chr2:179485523;179485522;179485521
Novex-1	6332	19219;19220;19221	chr2:178620796;178620795;178620794	chr2:179485523;179485522;179485521
Novex-2	6399	19420;19421;19422	chr2:178620796;178620795;178620794	chr2:179485523;179485522;179485521
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-104
• Domain position: 65
• Structural Position: 148
• Q(SASA): 0.7985
• 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
D/E	rs540340364	-0.103	0.007	N	0.183	0.083	0.0297737177859	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.94E-06	0
D/E	rs540340364	-0.103	0.007	N	0.183	0.083	0.0297737177859	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	0	None	None	0	1E-03	None	None	None	0	None
D/E	rs540340364	-0.103	0.007	N	0.183	0.083	0.0297737177859	gnomAD-4.0.0	1.59335E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86264E-06	0	0
D/G	None	None	0.001	N	0.135	0.148	0.146414634003	gnomAD-4.0.0	1.59333E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86261E-06	0	0
D/N	rs559878591	0.028	0.001	N	0.105	0.09	0.0954503805726	gnomAD-2.1.1	2.15E-05	None	None	None	None	N	None	0	0	None	0	3.08801E-04	None	0	None	0	0	0
D/N	rs559878591	0.028	0.001	N	0.105	0.09	0.0954503805726	gnomAD-3.1.2	3.29E-05	None	None	None	None	N	None	0	0	0	0	9.73141E-04	None	0	0	0	0	0
D/N	rs559878591	0.028	0.001	N	0.105	0.09	0.0954503805726	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	0	None	None	1E-03	0	None	None	None	0	None
D/N	rs559878591	0.028	0.001	N	0.105	0.09	0.0954503805726	gnomAD-4.0.0	8.68073E-06	None	None	None	None	N	None	0	6.67379E-05	None	0	2.23364E-04	None	0	0	0	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
D/A	0.1125	likely_benign	0.1245	benign	-0.209	Destabilizing	0.101	N	0.337	neutral	N	0.449184211	None	None	N
D/C	0.5732	likely_pathogenic	0.5892	pathogenic	0.014	Stabilizing	0.983	D	0.309	neutral	None	None	None	None	N
D/E	0.1338	likely_benign	0.1551	benign	-0.281	Destabilizing	0.007	N	0.183	neutral	N	0.42453775	None	None	N
D/F	0.5412	ambiguous	0.5526	ambiguous	-0.204	Destabilizing	0.94	D	0.321	neutral	None	None	None	None	N
D/G	0.1158	likely_benign	0.1207	benign	-0.372	Destabilizing	0.001	N	0.135	neutral	N	0.453121028	None	None	N
D/H	0.2218	likely_benign	0.2336	benign	0.104	Stabilizing	0.655	D	0.273	neutral	N	0.506476346	None	None	N
D/I	0.3151	likely_benign	0.3433	ambiguous	0.164	Stabilizing	0.836	D	0.339	neutral	None	None	None	None	N
D/K	0.2261	likely_benign	0.2436	benign	0.391	Stabilizing	0.002	N	0.182	neutral	None	None	None	None	N
D/L	0.3014	likely_benign	0.3219	benign	0.164	Stabilizing	0.418	N	0.368	neutral	None	None	None	None	N
D/M	0.5559	ambiguous	0.6047	pathogenic	0.222	Stabilizing	0.983	D	0.306	neutral	None	None	None	None	N
D/N	0.0909	likely_benign	0.0995	benign	0.092	Stabilizing	0.001	N	0.105	neutral	N	0.447929989	None	None	N
D/P	0.5219	ambiguous	0.5422	ambiguous	0.061	Stabilizing	0.836	D	0.327	neutral	None	None	None	None	N
D/Q	0.2465	likely_benign	0.2723	benign	0.117	Stabilizing	0.418	N	0.274	neutral	None	None	None	None	N
D/R	0.2568	likely_benign	0.2658	benign	0.561	Stabilizing	0.264	N	0.362	neutral	None	None	None	None	N
D/S	0.0989	likely_benign	0.1055	benign	0.002	Stabilizing	0.027	N	0.185	neutral	None	None	None	None	N
D/T	0.2066	likely_benign	0.2304	benign	0.133	Stabilizing	0.264	N	0.312	neutral	None	None	None	None	N
D/V	0.1816	likely_benign	0.1968	benign	0.061	Stabilizing	0.523	D	0.361	neutral	N	0.467997839	None	None	N
D/W	0.8205	likely_pathogenic	0.8252	pathogenic	-0.098	Destabilizing	0.983	D	0.382	neutral	None	None	None	None	N
D/Y	0.2039	likely_benign	0.2115	benign	0.028	Stabilizing	0.921	D	0.322	neutral	N	0.507817502	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.