TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6243	18952;18953;18954	chr2:178729429;178729428;178729427	chr2:179594156;179594155;179594154
N2AB	5926	18001;18002;18003	chr2:178729429;178729428;178729427	chr2:179594156;179594155;179594154
N2A	4999	15220;15221;15222	chr2:178729429;178729428;178729427	chr2:179594156;179594155;179594154
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: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-46
• Domain position: 45
• Structural Position: 102
• Q(SASA): 1.0012
• 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
K/E	rs764402049	-0.01	0.959	N	0.275	0.176	0.216624796971	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
K/E	rs764402049	-0.01	0.959	N	0.275	0.176	0.216624796971	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.06954E-04	0
K/E	rs764402049	-0.01	0.959	N	0.275	0.176	0.216624796971	gnomAD-4.0.0	5.12524E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	5.35977E-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
K/A	0.3322	likely_benign	0.4481	ambiguous	-0.092	Destabilizing	0.079	N	0.18	neutral	None	None	None	None	N
K/C	0.7912	likely_pathogenic	0.8537	pathogenic	-0.561	Destabilizing	0.999	D	0.292	neutral	None	None	None	None	N
K/D	0.4529	ambiguous	0.6075	pathogenic	-0.339	Destabilizing	0.969	D	0.361	neutral	None	None	None	None	N
K/E	0.1623	likely_benign	0.2492	benign	-0.365	Destabilizing	0.959	D	0.275	neutral	N	0.461304862	None	None	N
K/F	0.8119	likely_pathogenic	0.8864	pathogenic	-0.501	Destabilizing	0.982	D	0.336	neutral	None	None	None	None	N
K/G	0.3373	likely_benign	0.4496	ambiguous	-0.178	Destabilizing	0.939	D	0.351	neutral	None	None	None	None	N
K/H	0.3822	ambiguous	0.4767	ambiguous	-0.273	Destabilizing	0.999	D	0.315	neutral	None	None	None	None	N
K/I	0.4622	ambiguous	0.5794	pathogenic	0.052	Stabilizing	0.852	D	0.411	neutral	N	0.46335189	None	None	N
K/L	0.4363	ambiguous	0.5483	ambiguous	0.052	Stabilizing	0.046	N	0.263	neutral	None	None	None	None	N
K/M	0.3343	likely_benign	0.4288	ambiguous	-0.204	Destabilizing	0.982	D	0.309	neutral	None	None	None	None	N
K/N	0.3903	ambiguous	0.5442	ambiguous	-0.124	Destabilizing	0.959	D	0.303	neutral	N	0.487472743	None	None	N
K/P	0.4301	ambiguous	0.5511	ambiguous	0.024	Stabilizing	0.991	D	0.351	neutral	None	None	None	None	N
K/Q	0.1408	likely_benign	0.1817	benign	-0.258	Destabilizing	0.996	D	0.29	neutral	N	0.49482279	None	None	N
K/R	0.0793	likely_benign	0.0833	benign	-0.233	Destabilizing	0.959	D	0.279	neutral	N	0.439969585	None	None	N
K/S	0.3513	ambiguous	0.4856	ambiguous	-0.476	Destabilizing	0.759	D	0.283	neutral	None	None	None	None	N
K/T	0.2211	likely_benign	0.322	benign	-0.4	Destabilizing	0.134	N	0.246	neutral	N	0.470311135	None	None	N
K/V	0.407	ambiguous	0.5155	ambiguous	0.024	Stabilizing	0.759	D	0.304	neutral	None	None	None	None	N
K/W	0.7597	likely_pathogenic	0.8244	pathogenic	-0.614	Destabilizing	0.999	D	0.315	neutral	None	None	None	None	N
K/Y	0.6741	likely_pathogenic	0.7677	pathogenic	-0.275	Destabilizing	0.997	D	0.331	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.