TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32391	97396;97397;97398	chr2:178542683;178542682;178542681	chr2:179407410;179407409;179407408
N2AB	30750	92473;92474;92475	chr2:178542683;178542682;178542681	chr2:179407410;179407409;179407408
N2A	29823	89692;89693;89694	chr2:178542683;178542682;178542681	chr2:179407410;179407409;179407408
N2B	23326	70201;70202;70203	chr2:178542683;178542682;178542681	chr2:179407410;179407409;179407408
Novex-1	23451	70576;70577;70578	chr2:178542683;178542682;178542681	chr2:179407410;179407409;179407408
Novex-2	23518	70777;70778;70779	chr2:178542683;178542682;178542681	chr2:179407410;179407409;179407408
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: 85
• Structural Position: 171
• Q(SASA): 0.2844
• 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/I	rs1353755396	0.055	0.166	N	0.523	0.16	0.296329037015	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
T/I	rs1353755396	0.055	0.166	N	0.523	0.16	0.296329037015	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.42E-05	0	0	0	0	None	0	0	0	0	0
T/I	rs1353755396	0.055	0.166	N	0.523	0.16	0.296329037015	gnomAD-4.0.0	4.33914E-06	None	None	None	None	N	None	1.33583E-05	0	None	0	0	None	0	0	5.08718E-06	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
T/A	0.0821	likely_benign	0.0755	benign	-0.671	Destabilizing	0.001	N	0.145	neutral	N	0.491692924	None	None	N
T/C	0.3255	likely_benign	0.311	benign	-0.427	Destabilizing	0.991	D	0.583	neutral	None	None	None	None	N
T/D	0.3115	likely_benign	0.2821	benign	-0.223	Destabilizing	0.39	N	0.562	neutral	None	None	None	None	N
T/E	0.2412	likely_benign	0.2297	benign	-0.248	Destabilizing	0.39	N	0.569	neutral	None	None	None	None	N
T/F	0.255	likely_benign	0.2106	benign	-0.87	Destabilizing	0.818	D	0.655	neutral	None	None	None	None	N
T/G	0.2055	likely_benign	0.1902	benign	-0.9	Destabilizing	0.39	N	0.583	neutral	None	None	None	None	N
T/H	0.2069	likely_benign	0.1847	benign	-1.254	Destabilizing	0.901	D	0.631	neutral	None	None	None	None	N
T/I	0.112	likely_benign	0.1044	benign	-0.164	Destabilizing	0.166	N	0.523	neutral	N	0.514012423	None	None	N
T/K	0.1391	likely_benign	0.1272	benign	-0.692	Destabilizing	0.004	N	0.27	neutral	None	None	None	None	N
T/L	0.1015	likely_benign	0.088	benign	-0.164	Destabilizing	0.004	N	0.231	neutral	None	None	None	None	N
T/M	0.0788	likely_benign	0.0748	benign	0.132	Stabilizing	0.818	D	0.6	neutral	None	None	None	None	N
T/N	0.0973	likely_benign	0.0899	benign	-0.573	Destabilizing	0.003	N	0.287	neutral	N	0.485748387	None	None	N
T/P	0.1414	likely_benign	0.1172	benign	-0.301	Destabilizing	0.873	D	0.616	neutral	N	0.520285035	None	None	N
T/Q	0.1731	likely_benign	0.1654	benign	-0.774	Destabilizing	0.818	D	0.616	neutral	None	None	None	None	N
T/R	0.1372	likely_benign	0.1166	benign	-0.441	Destabilizing	0.39	N	0.587	neutral	None	None	None	None	N
T/S	0.1067	likely_benign	0.1001	benign	-0.81	Destabilizing	0.166	N	0.433	neutral	N	0.440744029	None	None	N
T/V	0.0948	likely_benign	0.0938	benign	-0.301	Destabilizing	0.002	N	0.147	neutral	None	None	None	None	N
T/W	0.5751	likely_pathogenic	0.523	ambiguous	-0.818	Destabilizing	0.991	D	0.655	neutral	None	None	None	None	N
T/Y	0.2656	likely_benign	0.2269	benign	-0.576	Destabilizing	0.965	D	0.649	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.