TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19429	58510;58511;58512	chr2:178594108;178594107;178594106	chr2:179458835;179458834;179458833
N2AB	17788	53587;53588;53589	chr2:178594108;178594107;178594106	chr2:179458835;179458834;179458833
N2A	16861	50806;50807;50808	chr2:178594108;178594107;178594106	chr2:179458835;179458834;179458833
N2B	10364	31315;31316;31317	chr2:178594108;178594107;178594106	chr2:179458835;179458834;179458833
Novex-1	10489	31690;31691;31692	chr2:178594108;178594107;178594106	chr2:179458835;179458834;179458833
Novex-2	10556	31891;31892;31893	chr2:178594108;178594107;178594106	chr2:179458835;179458834;179458833
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-118
• Domain position: 39
• Structural Position: 70
• Q(SASA): 0.3088
• 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/Q	None	None	0.31	N	0.19	0.176	0.346085882481	gnomAD-4.0.0	1.59204E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43287E-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	0.1003	likely_benign	0.1023	benign	-0.767	Destabilizing	0.061	N	0.161	neutral	N	0.451905172	None	None	N
E/C	0.7256	likely_pathogenic	0.7416	pathogenic	-0.303	Destabilizing	0.999	D	0.4	neutral	None	None	None	None	N
E/D	0.1729	likely_benign	0.1914	benign	-0.653	Destabilizing	0.826	D	0.249	neutral	N	0.513204347	None	None	N
E/F	0.6947	likely_pathogenic	0.7098	pathogenic	-0.443	Destabilizing	0.997	D	0.395	neutral	None	None	None	None	N
E/G	0.1322	likely_benign	0.1307	benign	-1.04	Destabilizing	0.015	N	0.205	neutral	N	0.485711101	None	None	N
E/H	0.4318	ambiguous	0.4387	ambiguous	-0.459	Destabilizing	0.991	D	0.32	neutral	None	None	None	None	N
E/I	0.2774	likely_benign	0.302	benign	-0.049	Destabilizing	0.991	D	0.413	neutral	None	None	None	None	N
E/K	0.1168	likely_benign	0.1171	benign	-0.316	Destabilizing	0.852	D	0.243	neutral	N	0.498234894	None	None	N
E/L	0.2659	likely_benign	0.2847	benign	-0.049	Destabilizing	0.939	D	0.365	neutral	None	None	None	None	N
E/M	0.3487	ambiguous	0.3725	ambiguous	0.251	Stabilizing	0.999	D	0.371	neutral	None	None	None	None	N
E/N	0.2686	likely_benign	0.2969	benign	-0.644	Destabilizing	0.969	D	0.275	neutral	None	None	None	None	N
E/P	0.2355	likely_benign	0.2442	benign	-0.268	Destabilizing	0.991	D	0.34	neutral	None	None	None	None	N
E/Q	0.1242	likely_benign	0.124	benign	-0.558	Destabilizing	0.31	N	0.19	neutral	N	0.515204502	None	None	N
E/R	0.2047	likely_benign	0.1985	benign	-0.021	Destabilizing	0.939	D	0.271	neutral	None	None	None	None	N
E/S	0.1747	likely_benign	0.1853	benign	-0.871	Destabilizing	0.759	D	0.252	neutral	None	None	None	None	N
E/T	0.1717	likely_benign	0.1857	benign	-0.652	Destabilizing	0.939	D	0.29	neutral	None	None	None	None	N
E/V	0.1635	likely_benign	0.1735	benign	-0.268	Destabilizing	0.92	D	0.333	neutral	N	0.513551064	None	None	N
E/W	0.8382	likely_pathogenic	0.8406	pathogenic	-0.223	Destabilizing	0.999	D	0.43	neutral	None	None	None	None	N
E/Y	0.5799	likely_pathogenic	0.599	pathogenic	-0.214	Destabilizing	0.997	D	0.377	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.