TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28535	85828;85829;85830	chr2:178560529;178560528;178560527	chr2:179425256;179425255;179425254
N2AB	26894	80905;80906;80907	chr2:178560529;178560528;178560527	chr2:179425256;179425255;179425254
N2A	25967	78124;78125;78126	chr2:178560529;178560528;178560527	chr2:179425256;179425255;179425254
N2B	19470	58633;58634;58635	chr2:178560529;178560528;178560527	chr2:179425256;179425255;179425254
Novex-1	19595	59008;59009;59010	chr2:178560529;178560528;178560527	chr2:179425256;179425255;179425254
Novex-2	19662	59209;59210;59211	chr2:178560529;178560528;178560527	chr2:179425256;179425255;179425254
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-95
• Domain position: 86
• Structural Position: 119
• Q(SASA): 0.3872
• 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	None	None	0.979	N	0.474	0.196	0.324161360171	gnomAD-4.0.0	6.84478E-07	None	None	None	None	N	None	0	0	None	0	0	None	1.87695E-05	0	0	0	0
E/K	rs538803059	-0.009	0.958	N	0.546	0.287	None	gnomAD-2.1.1	8.08E-06	None	None	None	None	N	None	6.47E-05	0	None	0	0	None	3.28E-05	None	0	0	0
E/K	rs538803059	-0.009	0.958	N	0.546	0.287	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
E/K	rs538803059	-0.009	0.958	N	0.546	0.287	None	gnomAD-4.0.0	2.56405E-06	None	None	None	None	N	None	1.69182E-05	0	None	0	0	None	0	0	0	1.34088E-05	0
E/Q	None	None	0.994	N	0.682	0.316	0.29527378943	gnomAD-4.0.0	1.59256E-06	None	None	None	None	N	None	0	0	None	0	2.78211E-05	None	0	0	0	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
E/A	0.1965	likely_benign	0.2053	benign	-0.63	Destabilizing	0.958	D	0.594	neutral	N	0.486510525	None	None	N
E/C	0.8351	likely_pathogenic	0.8505	pathogenic	-0.247	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
E/D	0.1221	likely_benign	0.1326	benign	-0.621	Destabilizing	0.979	D	0.474	neutral	N	0.492180422	None	None	N
E/F	0.7344	likely_pathogenic	0.7286	pathogenic	-0.381	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
E/G	0.242	likely_benign	0.2384	benign	-0.877	Destabilizing	0.988	D	0.703	prob.neutral	N	0.509703662	None	None	N
E/H	0.5218	ambiguous	0.5258	ambiguous	-0.307	Destabilizing	1.0	D	0.663	neutral	None	None	None	None	N
E/I	0.3152	likely_benign	0.3222	benign	0.005	Stabilizing	0.995	D	0.781	deleterious	None	None	None	None	N
E/K	0.1587	likely_benign	0.1459	benign	-0.062	Destabilizing	0.958	D	0.546	neutral	N	0.472774363	None	None	N
E/L	0.3678	ambiguous	0.3665	ambiguous	0.005	Stabilizing	0.991	D	0.747	deleterious	None	None	None	None	N
E/M	0.4354	ambiguous	0.4349	ambiguous	0.194	Stabilizing	1.0	D	0.76	deleterious	None	None	None	None	N
E/N	0.2839	likely_benign	0.2916	benign	-0.404	Destabilizing	0.995	D	0.704	prob.neutral	None	None	None	None	N
E/P	0.4269	ambiguous	0.4611	ambiguous	-0.186	Destabilizing	0.086	N	0.467	neutral	None	None	None	None	N
E/Q	0.155	likely_benign	0.1525	benign	-0.363	Destabilizing	0.994	D	0.682	prob.neutral	N	0.487751519	None	None	N
E/R	0.2854	likely_benign	0.2686	benign	0.211	Stabilizing	0.995	D	0.705	prob.neutral	None	None	None	None	N
E/S	0.2486	likely_benign	0.2551	benign	-0.605	Destabilizing	0.968	D	0.634	neutral	None	None	None	None	N
E/T	0.2908	likely_benign	0.2945	benign	-0.409	Destabilizing	0.991	D	0.713	prob.delet.	None	None	None	None	N
E/V	0.1922	likely_benign	0.1939	benign	-0.186	Destabilizing	0.994	D	0.727	prob.delet.	N	0.46844595	None	None	N
E/W	0.8994	likely_pathogenic	0.8992	pathogenic	-0.175	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
E/Y	0.5745	likely_pathogenic	0.5853	pathogenic	-0.137	Destabilizing	0.998	D	0.787	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.