TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25294	76105;76106;76107	chr2:178570252;178570251;178570250	chr2:179434979;179434978;179434977
N2AB	23653	71182;71183;71184	chr2:178570252;178570251;178570250	chr2:179434979;179434978;179434977
N2A	22726	68401;68402;68403	chr2:178570252;178570251;178570250	chr2:179434979;179434978;179434977
N2B	16229	48910;48911;48912	chr2:178570252;178570251;178570250	chr2:179434979;179434978;179434977
Novex-1	16354	49285;49286;49287	chr2:178570252;178570251;178570250	chr2:179434979;179434978;179434977
Novex-2	16421	49486;49487;49488	chr2:178570252;178570251;178570250	chr2:179434979;179434978;179434977
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: Fn3-71
• Domain position: 91
• Structural Position: 125
• Q(SASA): 0.4354
• 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	0.682	N	0.619	0.172	0.314716216878	gnomAD-4.0.0	1.59206E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85928E-06	0	0
E/Q	None	None	0.682	N	0.582	0.147	0.180583059064	gnomAD-4.0.0	1.59206E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85928E-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	0.0849	likely_benign	0.0898	benign	-0.119	Destabilizing	0.518	D	0.541	neutral	N	0.509627245	None	None	N
E/C	0.5798	likely_pathogenic	0.6343	pathogenic	-0.168	Destabilizing	0.996	D	0.791	deleterious	None	None	None	None	N
E/D	0.0738	likely_benign	0.0804	benign	-0.282	Destabilizing	0.003	N	0.227	neutral	N	0.490945484	None	None	N
E/F	0.4892	ambiguous	0.5184	ambiguous	-0.08	Destabilizing	0.984	D	0.784	deleterious	None	None	None	None	N
E/G	0.0903	likely_benign	0.0973	benign	-0.264	Destabilizing	0.682	D	0.619	neutral	N	0.466226996	None	None	N
E/H	0.2955	likely_benign	0.3037	benign	0.457	Stabilizing	0.953	D	0.614	neutral	None	None	None	None	N
E/I	0.1677	likely_benign	0.1829	benign	0.213	Stabilizing	0.953	D	0.781	deleterious	None	None	None	None	N
E/K	0.0862	likely_benign	0.085	benign	0.395	Stabilizing	0.007	N	0.246	neutral	N	0.475417255	None	None	N
E/L	0.1726	likely_benign	0.1903	benign	0.213	Stabilizing	0.909	D	0.722	deleterious	None	None	None	None	N
E/M	0.2377	likely_benign	0.2578	benign	0.043	Stabilizing	0.996	D	0.759	deleterious	None	None	None	None	N
E/N	0.1394	likely_benign	0.1474	benign	0.111	Stabilizing	0.587	D	0.541	neutral	None	None	None	None	N
E/P	0.1967	likely_benign	0.2235	benign	0.121	Stabilizing	0.953	D	0.644	neutral	None	None	None	None	N
E/Q	0.0942	likely_benign	0.0949	benign	0.132	Stabilizing	0.682	D	0.582	neutral	N	0.464074176	None	None	N
E/R	0.16	likely_benign	0.1615	benign	0.659	Stabilizing	0.587	D	0.553	neutral	None	None	None	None	N
E/S	0.1043	likely_benign	0.112	benign	-0.038	Destabilizing	0.74	D	0.481	neutral	None	None	None	None	N
E/T	0.1218	likely_benign	0.1293	benign	0.086	Stabilizing	0.74	D	0.605	neutral	None	None	None	None	N
E/V	0.1042	likely_benign	0.1145	benign	0.121	Stabilizing	0.883	D	0.704	prob.delet.	N	0.492053479	None	None	N
E/W	0.7587	likely_pathogenic	0.7823	pathogenic	0.007	Stabilizing	0.996	D	0.777	deleterious	None	None	None	None	N
E/Y	0.3866	ambiguous	0.4093	ambiguous	0.153	Stabilizing	0.984	D	0.765	deleterious	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.