TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16220	48883;48884;48885	chr2:178614949;178614948;178614947	chr2:179479676;179479675;179479674
N2AB	14579	43960;43961;43962	chr2:178614949;178614948;178614947	chr2:179479676;179479675;179479674
N2A	13652	41179;41180;41181	chr2:178614949;178614948;178614947	chr2:179479676;179479675;179479674
N2B	7155	21688;21689;21690	chr2:178614949;178614948;178614947	chr2:179479676;179479675;179479674
Novex-1	7280	22063;22064;22065	chr2:178614949;178614948;178614947	chr2:179479676;179479675;179479674
Novex-2	7347	22264;22265;22266	chr2:178614949;178614948;178614947	chr2:179479676;179479675;179479674
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: Fn3-5
• Domain position: 66
• Structural Position: 98
• Q(SASA): 0.5193
• 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/K	rs2057034942	None	0.006	N	0.091	0.166	0.253726318573	gnomAD-4.0.0	1.63263E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.92759E-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
E/A	0.1643	likely_benign	0.1616	benign	-0.421	Destabilizing	0.27	N	0.282	neutral	N	0.482636784	None	None	N
E/C	0.8107	likely_pathogenic	0.8198	pathogenic	-0.307	Destabilizing	0.995	D	0.253	neutral	None	None	None	None	N
E/D	0.1726	likely_benign	0.1837	benign	-0.538	Destabilizing	0.006	N	0.081	neutral	N	0.48430244	None	None	N
E/F	0.8424	likely_pathogenic	0.8283	pathogenic	0.093	Stabilizing	0.944	D	0.295	neutral	None	None	None	None	N
E/G	0.282	likely_benign	0.2822	benign	-0.687	Destabilizing	0.642	D	0.343	neutral	D	0.536299019	None	None	N
E/H	0.5198	ambiguous	0.5385	ambiguous	0.389	Stabilizing	0.944	D	0.301	neutral	None	None	None	None	N
E/I	0.2907	likely_benign	0.2776	benign	0.273	Stabilizing	0.013	N	0.175	neutral	None	None	None	None	N
E/K	0.1951	likely_benign	0.191	benign	0.201	Stabilizing	0.006	N	0.091	neutral	N	0.394529783	None	None	N
E/L	0.3649	ambiguous	0.3567	ambiguous	0.273	Stabilizing	0.329	N	0.31	neutral	None	None	None	None	N
E/M	0.4457	ambiguous	0.4319	ambiguous	0.263	Stabilizing	0.944	D	0.265	neutral	None	None	None	None	N
E/N	0.3306	likely_benign	0.3496	ambiguous	-0.429	Destabilizing	0.543	D	0.189	neutral	None	None	None	None	N
E/P	0.6449	likely_pathogenic	0.6166	pathogenic	0.063	Stabilizing	0.828	D	0.347	neutral	None	None	None	None	N
E/Q	0.1458	likely_benign	0.1475	benign	-0.32	Destabilizing	0.023	N	0.121	neutral	N	0.463159295	None	None	N
E/R	0.3254	likely_benign	0.3125	benign	0.575	Stabilizing	0.543	D	0.204	neutral	None	None	None	None	N
E/S	0.219	likely_benign	0.2309	benign	-0.582	Destabilizing	0.329	N	0.202	neutral	None	None	None	None	N
E/T	0.1711	likely_benign	0.1696	benign	-0.345	Destabilizing	0.013	N	0.081	neutral	None	None	None	None	N
E/V	0.1663	likely_benign	0.1597	benign	0.063	Stabilizing	0.023	N	0.129	neutral	N	0.461791897	None	None	N
E/W	0.9332	likely_pathogenic	0.9284	pathogenic	0.357	Stabilizing	0.995	D	0.273	neutral	None	None	None	None	N
E/Y	0.7453	likely_pathogenic	0.7439	pathogenic	0.371	Stabilizing	0.981	D	0.267	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.