TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29889	89890;89891;89892	chr2:178553235;178553234;178553233	chr2:179417962;179417961;179417960
N2AB	28248	84967;84968;84969	chr2:178553235;178553234;178553233	chr2:179417962;179417961;179417960
N2A	27321	82186;82187;82188	chr2:178553235;178553234;178553233	chr2:179417962;179417961;179417960
N2B	20824	62695;62696;62697	chr2:178553235;178553234;178553233	chr2:179417962;179417961;179417960
Novex-1	20949	63070;63071;63072	chr2:178553235;178553234;178553233	chr2:179417962;179417961;179417960
Novex-2	21016	63271;63272;63273	chr2:178553235;178553234;178553233	chr2:179417962;179417961;179417960
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-147
• Domain position: 48
• Structural Position: 125
• Q(SASA): 0.4887
• 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/D	rs1293413587	-0.326	0.003	N	0.179	0.047	0.248417906384	gnomAD-2.1.1	1.61E-05	None	None	None	None	N	None	0	5.79E-05	None	0	1.11346E-04	None	0	None	0	0	0
E/D	rs1293413587	-0.326	0.003	N	0.179	0.047	0.248417906384	gnomAD-4.0.0	5.47479E-06	None	None	None	None	N	None	0	4.47227E-05	None	0	1.51156E-04	None	0	0	0	0	0
E/K	rs1356821044	0.535	0.003	N	0.175	0.113	0.250039746154	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
E/K	rs1356821044	0.535	0.003	N	0.175	0.113	0.250039746154	gnomAD-4.0.0	2.0531E-06	None	None	None	None	N	None	0	2.23614E-05	None	0	0	None	0	0	0	1.15937E-05	1.65651E-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
E/A	0.1683	likely_benign	0.147	benign	-0.352	Destabilizing	0.001	N	0.263	neutral	N	0.485541426	None	None	N
E/C	0.7117	likely_pathogenic	0.6713	pathogenic	0.037	Stabilizing	0.497	N	0.384	neutral	None	None	None	None	N
E/D	0.1555	likely_benign	0.1422	benign	-0.274	Destabilizing	0.003	N	0.179	neutral	N	0.462620811	None	None	N
E/F	0.6434	likely_pathogenic	0.5829	pathogenic	-0.244	Destabilizing	0.022	N	0.505	neutral	None	None	None	None	N
E/G	0.205	likely_benign	0.1714	benign	-0.539	Destabilizing	0.006	N	0.306	neutral	N	0.494557554	None	None	N
E/H	0.2246	likely_benign	0.206	benign	-0.011	Destabilizing	None	N	0.093	neutral	None	None	None	None	N
E/I	0.2382	likely_benign	0.2089	benign	0.104	Stabilizing	0.009	N	0.447	neutral	None	None	None	None	N
E/K	0.0931	likely_benign	0.0889	benign	0.494	Stabilizing	0.003	N	0.175	neutral	N	0.498040106	None	None	N
E/L	0.2703	likely_benign	0.2319	benign	0.104	Stabilizing	None	N	0.243	neutral	None	None	None	None	N
E/M	0.3576	ambiguous	0.317	benign	0.203	Stabilizing	0.138	N	0.428	neutral	None	None	None	None	N
E/N	0.2045	likely_benign	0.1821	benign	0.108	Stabilizing	None	N	0.096	neutral	None	None	None	None	N
E/P	0.87	likely_pathogenic	0.796	pathogenic	-0.028	Destabilizing	0.037	N	0.391	neutral	None	None	None	None	N
E/Q	0.0686	likely_benign	0.0683	benign	0.148	Stabilizing	None	N	0.097	neutral	N	0.483161569	None	None	N
E/R	0.1323	likely_benign	0.1222	benign	0.637	Stabilizing	None	N	0.115	neutral	None	None	None	None	N
E/S	0.1727	likely_benign	0.1619	benign	-0.024	Destabilizing	0.001	N	0.12	neutral	None	None	None	None	N
E/T	0.1483	likely_benign	0.1383	benign	0.137	Stabilizing	None	N	0.147	neutral	None	None	None	None	N
E/V	0.176	likely_benign	0.1513	benign	-0.028	Destabilizing	0.007	N	0.328	neutral	D	0.522669192	None	None	N
E/W	0.7652	likely_pathogenic	0.6978	pathogenic	-0.092	Destabilizing	0.788	D	0.371	neutral	None	None	None	None	N
E/Y	0.4795	ambiguous	0.411	ambiguous	0.006	Stabilizing	0.044	N	0.479	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.