TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20455	61588;61589;61590	chr2:178590362;178590361;178590360	chr2:179455089;179455088;179455087
N2AB	18814	56665;56666;56667	chr2:178590362;178590361;178590360	chr2:179455089;179455088;179455087
N2A	17887	53884;53885;53886	chr2:178590362;178590361;178590360	chr2:179455089;179455088;179455087
N2B	11390	34393;34394;34395	chr2:178590362;178590361;178590360	chr2:179455089;179455088;179455087
Novex-1	11515	34768;34769;34770	chr2:178590362;178590361;178590360	chr2:179455089;179455088;179455087
Novex-2	11582	34969;34970;34971	chr2:178590362;178590361;178590360	chr2:179455089;179455088;179455087
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: Fn3-36
• Domain position: 85
• Structural Position: 117
• Q(SASA): 0.4549
• Predicted PPI site: I

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	rs1347430347	None	0.104	N	0.263	0.044	0.156986980423	gnomAD-2.1.1	3.19E-05	None	None	None	None	I	None	0	1.18203E-03	None	0	0	None	0	None	0	0	0
E/D	rs1347430347	None	0.104	N	0.263	0.044	0.156986980423	gnomAD-3.1.2	2.63E-05	None	None	None	None	I	None	9.65E-05	0	0	0	0	None	0	0	0	0	0
E/D	rs1347430347	None	0.104	N	0.263	0.044	0.156986980423	gnomAD-4.0.0	2.63054E-05	None	None	None	None	I	None	9.65251E-05	0	None	0	0	None	0	0	0	0	0
E/V	None	None	0.999	N	0.819	0.372	0.353761421236	gnomAD-4.0.0	7.01211E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.13232E-07	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	0.3301	likely_benign	0.3498	ambiguous	-0.299	Destabilizing	0.994	D	0.687	prob.neutral	N	0.469092918	None	None	I
E/C	0.9065	likely_pathogenic	0.9225	pathogenic	0.066	Stabilizing	1.0	D	0.797	deleterious	None	None	None	None	I
E/D	0.2935	likely_benign	0.2672	benign	-0.295	Destabilizing	0.104	N	0.263	neutral	N	0.461089511	None	None	I
E/F	0.8573	likely_pathogenic	0.8751	pathogenic	-0.134	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	I
E/G	0.5665	likely_pathogenic	0.5647	pathogenic	-0.496	Destabilizing	0.994	D	0.755	deleterious	N	0.514806565	None	None	I
E/H	0.8307	likely_pathogenic	0.8392	pathogenic	0.109	Stabilizing	1.0	D	0.797	deleterious	None	None	None	None	I
E/I	0.4087	ambiguous	0.4008	ambiguous	0.185	Stabilizing	1.0	D	0.831	deleterious	None	None	None	None	I
E/K	0.5167	ambiguous	0.5019	ambiguous	0.584	Stabilizing	0.994	D	0.665	neutral	N	0.483214222	None	None	I
E/L	0.5516	ambiguous	0.5419	ambiguous	0.185	Stabilizing	1.0	D	0.818	deleterious	None	None	None	None	I
E/M	0.598	likely_pathogenic	0.6185	pathogenic	0.27	Stabilizing	1.0	D	0.833	deleterious	None	None	None	None	I
E/N	0.6505	likely_pathogenic	0.6292	pathogenic	0.151	Stabilizing	0.998	D	0.766	deleterious	None	None	None	None	I
E/P	0.7258	likely_pathogenic	0.7506	pathogenic	0.044	Stabilizing	1.0	D	0.802	deleterious	None	None	None	None	I
E/Q	0.3751	ambiguous	0.3905	ambiguous	0.19	Stabilizing	0.998	D	0.732	prob.delet.	N	0.442791751	None	None	I
E/R	0.6939	likely_pathogenic	0.6946	pathogenic	0.74	Stabilizing	0.999	D	0.799	deleterious	None	None	None	None	I
E/S	0.523	ambiguous	0.5219	ambiguous	0.017	Stabilizing	0.992	D	0.669	neutral	None	None	None	None	I
E/T	0.4609	ambiguous	0.4619	ambiguous	0.19	Stabilizing	0.999	D	0.757	deleterious	None	None	None	None	I
E/V	0.2597	likely_benign	0.2646	benign	0.044	Stabilizing	0.999	D	0.819	deleterious	N	0.430035885	None	None	I
E/W	0.9597	likely_pathogenic	0.9675	pathogenic	0.038	Stabilizing	1.0	D	0.786	deleterious	None	None	None	None	I
E/Y	0.8288	likely_pathogenic	0.8394	pathogenic	0.133	Stabilizing	1.0	D	0.828	deleterious	None	None	None	None	I

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.