TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4722	14389;14390;14391	chr2:178738289;178738288;178738287	chr2:179603016;179603015;179603014
N2AB	4405	13438;13439;13440	chr2:178738289;178738288;178738287	chr2:179603016;179603015;179603014
N2A	3478	10657;10658;10659	chr2:178738289;178738288;178738287	chr2:179603016;179603015;179603014
N2B	4359	13300;13301;13302	chr2:178738289;178738288;178738287	chr2:179603016;179603015;179603014
Novex-1	4484	13675;13676;13677	chr2:178738289;178738288;178738287	chr2:179603016;179603015;179603014
Novex-2	4551	13876;13877;13878	chr2:178738289;178738288;178738287	chr2:179603016;179603015;179603014
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: Ig-30
• Domain position: 23
• Structural Position: 34
• Q(SASA): 0.6856
• 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/K	rs767604791	-0.482	0.992	N	0.521	0.312	0.312306559268	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
E/K	rs767604791	-0.482	0.992	N	0.521	0.312	0.312306559268	gnomAD-4.0.0	1.59206E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43336E-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
E/A	0.3678	ambiguous	0.4016	ambiguous	-1.034	Destabilizing	0.996	D	0.615	neutral	N	0.492248918	None	None	N
E/C	0.9607	likely_pathogenic	0.9608	pathogenic	-0.675	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
E/D	0.5349	ambiguous	0.5501	ambiguous	-1.442	Destabilizing	0.996	D	0.453	neutral	N	0.49237478	None	None	N
E/F	0.9283	likely_pathogenic	0.9358	pathogenic	-0.552	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
E/G	0.5847	likely_pathogenic	0.596	pathogenic	-1.432	Destabilizing	0.999	D	0.726	prob.delet.	N	0.493701351	None	None	N
E/H	0.762	likely_pathogenic	0.7767	pathogenic	-0.842	Destabilizing	1.0	D	0.71	prob.delet.	None	None	None	None	N
E/I	0.6025	likely_pathogenic	0.6595	pathogenic	0.072	Stabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
E/K	0.3914	ambiguous	0.3882	ambiguous	-1.043	Destabilizing	0.992	D	0.521	neutral	N	0.48969392	None	None	N
E/L	0.7301	likely_pathogenic	0.7666	pathogenic	0.072	Stabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
E/M	0.6699	likely_pathogenic	0.6995	pathogenic	0.6	Stabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
E/N	0.6639	likely_pathogenic	0.6913	pathogenic	-1.429	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
E/P	0.9867	likely_pathogenic	0.9875	pathogenic	-0.277	Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
E/Q	0.2142	likely_benign	0.2283	benign	-1.262	Destabilizing	0.957	D	0.33	neutral	N	0.490848369	None	None	N
E/R	0.569	likely_pathogenic	0.5611	ambiguous	-0.805	Destabilizing	0.999	D	0.725	prob.delet.	None	None	None	None	N
E/S	0.4716	ambiguous	0.488	ambiguous	-1.879	Destabilizing	0.997	D	0.587	neutral	None	None	None	None	N
E/T	0.4886	ambiguous	0.5081	ambiguous	-1.539	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
E/V	0.3901	ambiguous	0.4507	ambiguous	-0.277	Destabilizing	0.999	D	0.771	deleterious	N	0.493701351	None	None	N
E/W	0.9812	likely_pathogenic	0.9792	pathogenic	-0.404	Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	N
E/Y	0.8899	likely_pathogenic	0.9008	pathogenic	-0.313	Destabilizing	1.0	D	0.786	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.