TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6217	18874;18875;18876	chr2:178729507;178729506;178729505	chr2:179594234;179594233;179594232
N2AB	5900	17923;17924;17925	chr2:178729507;178729506;178729505	chr2:179594234;179594233;179594232
N2A	4973	15142;15143;15144	chr2:178729507;178729506;178729505	chr2:179594234;179594233;179594232
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-46
• Domain position: 19
• Structural Position: 29
• Q(SASA): 0.6487
• 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
E/G	None	None	0.014	N	0.421	0.208	0.190952846119	gnomAD-4.0.0	1.36862E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99578E-07	1.15942E-05	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
E/A	0.0887	likely_benign	0.0964	benign	-0.715	Destabilizing	0.003	N	0.347	neutral	N	0.467694904	None	None	N
E/C	0.5267	ambiguous	0.6147	pathogenic	-0.434	Destabilizing	None	N	0.423	neutral	None	None	None	None	N
E/D	0.117	likely_benign	0.1307	benign	-1.035	Destabilizing	None	N	0.234	neutral	N	0.477642539	None	None	N
E/F	0.3142	likely_benign	0.3667	ambiguous	-0.343	Destabilizing	0.022	N	0.525	neutral	None	None	None	None	N
E/G	0.1214	likely_benign	0.1327	benign	-1.044	Destabilizing	0.014	N	0.421	neutral	N	0.469859576	None	None	N
E/H	0.1968	likely_benign	0.2299	benign	-0.623	Destabilizing	None	N	0.369	neutral	None	None	None	None	N
E/I	0.1113	likely_benign	0.1337	benign	0.169	Stabilizing	0.003	N	0.441	neutral	None	None	None	None	N
E/K	0.0853	likely_benign	0.0924	benign	-0.726	Destabilizing	None	N	0.251	neutral	N	0.406222371	None	None	N
E/L	0.1327	likely_benign	0.1501	benign	0.169	Stabilizing	None	N	0.453	neutral	None	None	None	None	N
E/M	0.1707	likely_benign	0.1914	benign	0.518	Stabilizing	0.002	N	0.402	neutral	None	None	None	None	N
E/N	0.1372	likely_benign	0.1632	benign	-1.025	Destabilizing	0.018	N	0.425	neutral	None	None	None	None	N
E/P	0.5924	likely_pathogenic	0.6063	pathogenic	-0.104	Destabilizing	0.085	N	0.499	neutral	None	None	None	None	N
E/Q	0.0792	likely_benign	0.085	benign	-0.9	Destabilizing	None	N	0.248	neutral	N	0.453418885	None	None	N
E/R	0.1287	likely_benign	0.1381	benign	-0.448	Destabilizing	0.009	N	0.429	neutral	None	None	None	None	N
E/S	0.1055	likely_benign	0.1219	benign	-1.295	Destabilizing	0.009	N	0.347	neutral	None	None	None	None	N
E/T	0.0944	likely_benign	0.1098	benign	-1.039	Destabilizing	None	N	0.263	neutral	None	None	None	None	N
E/V	0.0818	likely_benign	0.0924	benign	-0.104	Destabilizing	None	N	0.351	neutral	N	0.421343752	None	None	N
E/W	0.5795	likely_pathogenic	0.6224	pathogenic	-0.191	Destabilizing	0.55	D	0.453	neutral	None	None	None	None	N
E/Y	0.2785	likely_benign	0.3268	benign	-0.146	Destabilizing	0.001	N	0.363	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.