TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8834	26725;26726;26727	chr2:178714158;178714157;178714156	chr2:179578885;179578884;179578883
N2AB	8517	25774;25775;25776	chr2:178714158;178714157;178714156	chr2:179578885;179578884;179578883
N2A	7590	22993;22994;22995	chr2:178714158;178714157;178714156	chr2:179578885;179578884;179578883
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: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-74
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.4197
• 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	0.92	D	0.377	0.31	0.533997809139	gnomAD-4.0.0	1.5988E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.44957E-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	0.1985	likely_benign	0.2208	benign	-0.409	Destabilizing	0.704	D	0.349	neutral	D	0.529517807	None	None	N
E/C	0.8549	likely_pathogenic	0.8796	pathogenic	-0.09	Destabilizing	0.999	D	0.462	neutral	None	None	None	None	N
E/D	0.1417	likely_benign	0.1533	benign	-0.443	Destabilizing	0.015	N	0.091	neutral	N	0.474453958	None	None	N
E/F	0.7877	likely_pathogenic	0.8032	pathogenic	-0.259	Destabilizing	0.997	D	0.434	neutral	None	None	None	None	N
E/G	0.1618	likely_benign	0.1736	benign	-0.623	Destabilizing	0.92	D	0.377	neutral	D	0.532462111	None	None	N
E/H	0.4771	ambiguous	0.501	ambiguous	-0.046	Destabilizing	0.997	D	0.356	neutral	None	None	None	None	N
E/I	0.4777	ambiguous	0.5058	ambiguous	0.127	Stabilizing	0.991	D	0.449	neutral	None	None	None	None	N
E/K	0.1529	likely_benign	0.1659	benign	0.227	Stabilizing	0.134	N	0.124	neutral	N	0.471008221	None	None	N
E/L	0.4813	ambiguous	0.5135	ambiguous	0.127	Stabilizing	0.969	D	0.385	neutral	None	None	None	None	N
E/M	0.5363	ambiguous	0.578	pathogenic	0.217	Stabilizing	0.999	D	0.424	neutral	None	None	None	None	N
E/N	0.2836	likely_benign	0.3138	benign	-0.11	Destabilizing	0.939	D	0.259	neutral	None	None	None	None	N
E/P	0.9201	likely_pathogenic	0.9252	pathogenic	-0.031	Destabilizing	0.991	D	0.392	neutral	None	None	None	None	N
E/Q	0.1426	likely_benign	0.1497	benign	-0.072	Destabilizing	0.92	D	0.347	neutral	N	0.48526281	None	None	N
E/R	0.2515	likely_benign	0.2563	benign	0.468	Stabilizing	0.884	D	0.309	neutral	None	None	None	None	N
E/S	0.2213	likely_benign	0.2464	benign	-0.277	Destabilizing	0.373	N	0.141	neutral	None	None	None	None	N
E/T	0.2553	likely_benign	0.285	benign	-0.105	Destabilizing	0.884	D	0.332	neutral	None	None	None	None	N
E/V	0.2847	likely_benign	0.3144	benign	-0.031	Destabilizing	0.959	D	0.401	neutral	N	0.493405078	None	None	N
E/W	0.8764	likely_pathogenic	0.8957	pathogenic	-0.102	Destabilizing	0.999	D	0.538	neutral	None	None	None	None	N
E/Y	0.6427	likely_pathogenic	0.6739	pathogenic	-0.015	Destabilizing	0.997	D	0.429	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.