TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5596	17011;17012;17013	chr2:178732183;178732182;178732181	chr2:179596910;179596909;179596908
N2AB	5279	16060;16061;16062	chr2:178732183;178732182;178732181	chr2:179596910;179596909;179596908
N2A	4352	13279;13280;13281	chr2:178732183;178732182;178732181	chr2:179596910;179596909;179596908
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-39
• Domain position: 54
• Structural Position: 131
• Q(SASA): 0.8739
• 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/A	None	None	0.042	N	0.257	0.078	0.183819452728	gnomAD-4.0.0	4.78939E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.29627E-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	0.104	likely_benign	0.1127	benign	0.008	Stabilizing	0.042	N	0.257	neutral	N	0.444434042	None	None	N
E/C	0.6772	likely_pathogenic	0.7144	pathogenic	-0.188	Destabilizing	0.958	D	0.169	neutral	None	None	None	None	N
E/D	0.0655	likely_benign	0.0659	benign	-0.433	Destabilizing	None	N	0.104	neutral	N	0.338997301	None	None	N
E/F	0.6166	likely_pathogenic	0.6528	pathogenic	-0.08	Destabilizing	0.859	D	0.2	neutral	None	None	None	None	N
E/G	0.0668	likely_benign	0.0702	benign	-0.082	Destabilizing	None	N	0.125	neutral	N	0.402216486	None	None	N
E/H	0.2698	likely_benign	0.2992	benign	0.515	Stabilizing	0.667	D	0.206	neutral	None	None	None	None	N
E/I	0.4234	ambiguous	0.4658	ambiguous	0.183	Stabilizing	0.667	D	0.262	neutral	None	None	None	None	N
E/K	0.1162	likely_benign	0.1248	benign	0.41	Stabilizing	None	N	0.137	neutral	N	0.46149965	None	None	N
E/L	0.3363	likely_benign	0.3863	ambiguous	0.183	Stabilizing	0.22	N	0.321	neutral	None	None	None	None	N
E/M	0.4178	ambiguous	0.4623	ambiguous	-0.019	Destabilizing	0.859	D	0.181	neutral	None	None	None	None	N
E/N	0.1092	likely_benign	0.1109	benign	0.157	Stabilizing	None	N	0.102	neutral	None	None	None	None	N
E/P	0.3585	ambiguous	0.3805	ambiguous	0.141	Stabilizing	0.364	N	0.338	neutral	None	None	None	None	N
E/Q	0.1089	likely_benign	0.1161	benign	0.163	Stabilizing	0.175	N	0.245	neutral	N	0.427541792	None	None	N
E/R	0.1705	likely_benign	0.1828	benign	0.582	Stabilizing	0.124	N	0.216	neutral	None	None	None	None	N
E/S	0.1084	likely_benign	0.1155	benign	0.055	Stabilizing	0.055	N	0.178	neutral	None	None	None	None	N
E/T	0.1967	likely_benign	0.217	benign	0.141	Stabilizing	0.104	N	0.266	neutral	None	None	None	None	N
E/V	0.2616	likely_benign	0.2873	benign	0.141	Stabilizing	0.301	N	0.318	neutral	N	0.462713159	None	None	N
E/W	0.7535	likely_pathogenic	0.7755	pathogenic	-0.063	Destabilizing	0.958	D	0.168	neutral	None	None	None	None	N
E/Y	0.4158	ambiguous	0.4363	ambiguous	0.13	Stabilizing	0.859	D	0.21	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.