TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8473	25642;25643;25644	chr2:178717317;178717316;178717315	chr2:179582044;179582043;179582042
N2AB	8156	24691;24692;24693	chr2:178717317;178717316;178717315	chr2:179582044;179582043;179582042
N2A	7229	21910;21911;21912	chr2:178717317;178717316;178717315	chr2:179582044;179582043;179582042
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: G
• RefSeq wild type transcript codon: GGT
• RefSeq wild type template codon: CCA
• Domain: Ig-70
• Domain position: 18
• Structural Position: 28
• Q(SASA): 0.1279
• 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/S	rs769092741	-0.73	0.713	N	0.633	0.179	0.101711395817	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
G/S	rs769092741	-0.73	0.713	N	0.633	0.179	0.101711395817	gnomAD-4.0.0	7.95902E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.42979E-05	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	0.0883	likely_benign	0.0863	benign	-0.325	Destabilizing	0.006	N	0.235	neutral	N	0.33372198	None	None	N
G/C	0.3364	likely_benign	0.3014	benign	-0.939	Destabilizing	0.999	D	0.74	deleterious	N	0.460806217	None	None	N
G/D	0.8499	likely_pathogenic	0.8082	pathogenic	0.19	Stabilizing	0.987	D	0.747	deleterious	N	0.50434635	None	None	N
G/E	0.8057	likely_pathogenic	0.7559	pathogenic	0.18	Stabilizing	0.992	D	0.727	prob.delet.	None	None	None	None	N
G/F	0.8819	likely_pathogenic	0.8406	pathogenic	-0.556	Destabilizing	0.996	D	0.764	deleterious	None	None	None	None	N
G/H	0.887	likely_pathogenic	0.8512	pathogenic	-0.864	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
G/I	0.4863	ambiguous	0.4375	ambiguous	0.169	Stabilizing	0.538	D	0.581	neutral	None	None	None	None	N
G/K	0.908	likely_pathogenic	0.8735	pathogenic	-0.634	Destabilizing	0.992	D	0.726	prob.delet.	None	None	None	None	N
G/L	0.6538	likely_pathogenic	0.6109	pathogenic	0.169	Stabilizing	0.886	D	0.613	neutral	None	None	None	None	N
G/M	0.7245	likely_pathogenic	0.6792	pathogenic	-0.196	Destabilizing	0.996	D	0.756	deleterious	None	None	None	None	N
G/N	0.8	likely_pathogenic	0.7517	pathogenic	-0.463	Destabilizing	0.996	D	0.688	prob.neutral	None	None	None	None	N
G/P	0.9816	likely_pathogenic	0.9748	pathogenic	0.048	Stabilizing	0.99	D	0.739	prob.delet.	None	None	None	None	N
G/Q	0.8044	likely_pathogenic	0.7617	pathogenic	-0.445	Destabilizing	0.996	D	0.719	prob.delet.	None	None	None	None	N
G/R	0.8045	likely_pathogenic	0.7597	pathogenic	-0.619	Destabilizing	0.995	D	0.747	deleterious	N	0.503999634	None	None	N
G/S	0.1377	likely_benign	0.1366	benign	-0.921	Destabilizing	0.713	D	0.633	neutral	N	0.49322528	None	None	N
G/T	0.2883	likely_benign	0.2663	benign	-0.791	Destabilizing	0.974	D	0.675	neutral	None	None	None	None	N
G/V	0.2911	likely_benign	0.2705	benign	0.048	Stabilizing	0.138	N	0.514	neutral	N	0.328505375	None	None	N
G/W	0.8717	likely_pathogenic	0.8279	pathogenic	-0.912	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
G/Y	0.8501	likely_pathogenic	0.8009	pathogenic	-0.426	Destabilizing	0.999	D	0.749	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.