TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19839	59740;59741;59742	chr2:178592490;178592489;178592488	chr2:179457217;179457216;179457215
N2AB	18198	54817;54818;54819	chr2:178592490;178592489;178592488	chr2:179457217;179457216;179457215
N2A	17271	52036;52037;52038	chr2:178592490;178592489;178592488	chr2:179457217;179457216;179457215
N2B	10774	32545;32546;32547	chr2:178592490;178592489;178592488	chr2:179457217;179457216;179457215
Novex-1	10899	32920;32921;32922	chr2:178592490;178592489;178592488	chr2:179457217;179457216;179457215
Novex-2	10966	33121;33122;33123	chr2:178592490;178592489;178592488	chr2:179457217;179457216;179457215
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGT
• RefSeq wild type template codon: CCA
• Domain: Ig-119
• Domain position: 50
• Structural Position: 135
• Q(SASA): 0.258
• 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
G/D	rs1256321814	0.192	0.467	N	0.341	0.234	0.144782658237	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
G/D	rs1256321814	0.192	0.467	N	0.341	0.234	0.144782658237	gnomAD-4.0.0	2.05296E-06	None	None	None	None	N	None	0	2.23664E-05	None	0	0	None	0	0	1.79917E-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
G/A	0.233	likely_benign	0.2126	benign	-0.292	Destabilizing	0.992	D	0.476	neutral	N	0.457634806	None	None	N
G/C	0.4548	ambiguous	0.4029	ambiguous	-0.728	Destabilizing	1.0	D	0.699	prob.neutral	N	0.479159329	None	None	N
G/D	0.8289	likely_pathogenic	0.7949	pathogenic	-0.381	Destabilizing	0.467	N	0.341	neutral	N	0.472026075	None	None	N
G/E	0.7456	likely_pathogenic	0.7095	pathogenic	-0.365	Destabilizing	0.996	D	0.633	neutral	None	None	None	None	N
G/F	0.8173	likely_pathogenic	0.7797	pathogenic	-0.503	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	N
G/H	0.8375	likely_pathogenic	0.8098	pathogenic	-1.112	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	N
G/I	0.7024	likely_pathogenic	0.6657	pathogenic	0.307	Stabilizing	0.998	D	0.748	deleterious	None	None	None	None	N
G/K	0.9206	likely_pathogenic	0.908	pathogenic	-0.764	Destabilizing	0.998	D	0.687	prob.neutral	None	None	None	None	N
G/L	0.7855	likely_pathogenic	0.7521	pathogenic	0.307	Stabilizing	0.998	D	0.721	prob.delet.	None	None	None	None	N
G/M	0.7869	likely_pathogenic	0.7563	pathogenic	0.046	Stabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
G/N	0.8025	likely_pathogenic	0.7462	pathogenic	-0.614	Destabilizing	0.998	D	0.75	deleterious	None	None	None	None	N
G/P	0.9955	likely_pathogenic	0.995	pathogenic	0.153	Stabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
G/Q	0.787	likely_pathogenic	0.7577	pathogenic	-0.603	Destabilizing	0.999	D	0.72	prob.delet.	None	None	None	None	N
G/R	0.8288	likely_pathogenic	0.8043	pathogenic	-0.772	Destabilizing	0.999	D	0.723	prob.delet.	N	0.51541428	None	None	N
G/S	0.2704	likely_benign	0.2259	benign	-0.996	Destabilizing	0.984	D	0.585	neutral	N	0.459078208	None	None	N
G/T	0.4315	ambiguous	0.3945	ambiguous	-0.862	Destabilizing	0.833	D	0.412	neutral	None	None	None	None	N
G/V	0.588	likely_pathogenic	0.547	ambiguous	0.153	Stabilizing	0.998	D	0.72	prob.delet.	N	0.493385569	None	None	N
G/W	0.7785	likely_pathogenic	0.7647	pathogenic	-1.015	Destabilizing	1.0	D	0.672	neutral	None	None	None	None	N
G/Y	0.7574	likely_pathogenic	0.7152	pathogenic	-0.463	Destabilizing	1.0	D	0.747	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.