TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9316	28171;28172;28173	chr2:178711290;178711289;178711288	chr2:179576017;179576016;179576015
N2AB	8999	27220;27221;27222	chr2:178711290;178711289;178711288	chr2:179576017;179576016;179576015
N2A	8072	24439;24440;24441	chr2:178711290;178711289;178711288	chr2:179576017;179576016;179576015
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: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-79
• Domain position: 16
• Structural Position: 25
• Q(SASA): 0.4236
• 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
L/P	None	None	0.996	N	0.393	0.237	0.733431072442	gnomAD-4.0.0	6.84352E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99622E-07	0	0
L/R	rs78643968	0.015	0.92	N	0.353	0.207	None	gnomAD-2.1.1	1.35641E-04	None	None	None	None	I	None	0	0	None	0	1.89452E-03	None	0	None	0	0	1.40489E-04
L/R	rs78643968	0.015	0.92	N	0.353	0.207	None	gnomAD-3.1.2	3.28E-05	None	None	None	None	I	None	0	0	0	0	9.61538E-04	None	0	0	0	0	0
L/R	rs78643968	0.015	0.92	N	0.353	0.207	None	gnomAD-4.0.0	2.04514E-05	None	None	None	None	I	None	0	0	None	0	6.90669E-04	None	0	0	0	0	3.20133E-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
L/A	0.1906	likely_benign	0.2473	benign	-0.957	Destabilizing	0.863	D	0.286	neutral	None	None	None	None	I
L/C	0.4943	ambiguous	0.5356	ambiguous	-0.625	Destabilizing	0.999	D	0.333	neutral	None	None	None	None	I
L/D	0.4283	ambiguous	0.5373	ambiguous	-0.357	Destabilizing	0.884	D	0.339	neutral	None	None	None	None	I
L/E	0.1912	likely_benign	0.246	benign	-0.44	Destabilizing	0.17	N	0.233	neutral	None	None	None	None	I
L/F	0.0924	likely_benign	0.0986	benign	-0.878	Destabilizing	0.997	D	0.287	neutral	None	None	None	None	I
L/G	0.3409	ambiguous	0.4373	ambiguous	-1.158	Destabilizing	0.046	N	0.225	neutral	None	None	None	None	I
L/H	0.1268	likely_benign	0.1468	benign	-0.411	Destabilizing	0.991	D	0.363	neutral	None	None	None	None	I
L/I	0.1111	likely_benign	0.1181	benign	-0.535	Destabilizing	0.99	D	0.272	neutral	None	None	None	None	I
L/K	0.1259	likely_benign	0.1733	benign	-0.51	Destabilizing	0.884	D	0.321	neutral	None	None	None	None	I
L/M	0.1033	likely_benign	0.1047	benign	-0.376	Destabilizing	0.996	D	0.305	neutral	N	0.450031863	None	None	I
L/N	0.1734	likely_benign	0.2256	benign	-0.27	Destabilizing	0.969	D	0.384	neutral	None	None	None	None	I
L/P	0.7214	likely_pathogenic	0.8566	pathogenic	-0.642	Destabilizing	0.996	D	0.393	neutral	N	0.489550256	None	None	I
L/Q	0.0802	likely_benign	0.1009	benign	-0.529	Destabilizing	0.31	N	0.173	neutral	N	0.379995775	None	None	I
L/R	0.107	likely_benign	0.1122	benign	0.102	Stabilizing	0.92	D	0.353	neutral	N	0.446836842	None	None	I
L/S	0.1398	likely_benign	0.174	benign	-0.781	Destabilizing	0.939	D	0.297	neutral	None	None	None	None	I
L/T	0.184	likely_benign	0.2284	benign	-0.755	Destabilizing	0.969	D	0.264	neutral	None	None	None	None	I
L/V	0.1183	likely_benign	0.1333	benign	-0.642	Destabilizing	0.959	D	0.232	neutral	N	0.503460916	None	None	I
L/W	0.1792	likely_benign	0.2182	benign	-0.876	Destabilizing	0.999	D	0.387	neutral	None	None	None	None	I
L/Y	0.1977	likely_benign	0.229	benign	-0.636	Destabilizing	0.997	D	0.31	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.