TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24683	74272;74273;74274	chr2:178572085;178572084;178572083	chr2:179436812;179436811;179436810
N2AB	23042	69349;69350;69351	chr2:178572085;178572084;178572083	chr2:179436812;179436811;179436810
N2A	22115	66568;66569;66570	chr2:178572085;178572084;178572083	chr2:179436812;179436811;179436810
N2B	15618	47077;47078;47079	chr2:178572085;178572084;178572083	chr2:179436812;179436811;179436810
Novex-1	15743	47452;47453;47454	chr2:178572085;178572084;178572083	chr2:179436812;179436811;179436810
Novex-2	15810	47653;47654;47655	chr2:178572085;178572084;178572083	chr2:179436812;179436811;179436810
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-67
• Domain position: 68
• Structural Position: 102
• Q(SASA): 0.1815
• 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/A	rs1708407970	None	0.524	N	0.475	0.232	0.26547132957	gnomAD-4.0.0	3.18489E-06	None	None	None	None	N	None	0	0	None	0	5.56917E-05	None	0	0	0	0	0
E/K	rs755064877	-0.94	0.892	N	0.542	0.294	0.266385636622	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	0	None	9.82E-05	None	0	0	0
E/K	rs755064877	-0.94	0.892	N	0.542	0.294	0.266385636622	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.07039E-04	0
E/K	rs755064877	-0.94	0.892	N	0.542	0.294	0.266385636622	gnomAD-4.0.0	6.40999E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.70241E-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	0.3221	likely_benign	0.2746	benign	-0.753	Destabilizing	0.524	D	0.475	neutral	N	0.48569438	None	None	N
E/C	0.9391	likely_pathogenic	0.9239	pathogenic	-0.443	Destabilizing	0.996	D	0.738	prob.delet.	None	None	None	None	N
E/D	0.325	likely_benign	0.3178	benign	-0.987	Destabilizing	0.637	D	0.446	neutral	N	0.510688825	None	None	N
E/F	0.9364	likely_pathogenic	0.9155	pathogenic	0.041	Stabilizing	0.95	D	0.743	deleterious	None	None	None	None	N
E/G	0.3184	likely_benign	0.2944	benign	-1.144	Destabilizing	0.981	D	0.651	neutral	N	0.496759522	None	None	N
E/H	0.7605	likely_pathogenic	0.7151	pathogenic	-0.148	Destabilizing	0.997	D	0.621	neutral	None	None	None	None	N
E/I	0.7069	likely_pathogenic	0.6459	pathogenic	0.321	Stabilizing	0.816	D	0.686	prob.neutral	None	None	None	None	N
E/K	0.3086	likely_benign	0.2609	benign	-0.539	Destabilizing	0.892	D	0.542	neutral	N	0.451293805	None	None	N
E/L	0.7395	likely_pathogenic	0.6809	pathogenic	0.321	Stabilizing	0.559	D	0.675	prob.neutral	None	None	None	None	N
E/M	0.6593	likely_pathogenic	0.5908	pathogenic	0.681	Stabilizing	0.924	D	0.689	prob.neutral	None	None	None	None	N
E/N	0.4385	ambiguous	0.4058	ambiguous	-1.13	Destabilizing	0.962	D	0.652	neutral	None	None	None	None	N
E/P	0.9892	likely_pathogenic	0.9866	pathogenic	-0.015	Destabilizing	0.891	D	0.662	neutral	None	None	None	None	N
E/Q	0.2026	likely_benign	0.1707	benign	-0.951	Destabilizing	0.984	D	0.657	neutral	N	0.453699391	None	None	N
E/R	0.5288	ambiguous	0.4674	ambiguous	-0.183	Destabilizing	0.975	D	0.645	neutral	None	None	None	None	N
E/S	0.3616	ambiguous	0.3106	benign	-1.442	Destabilizing	0.855	D	0.597	neutral	None	None	None	None	N
E/T	0.433	ambiguous	0.3661	ambiguous	-1.11	Destabilizing	0.934	D	0.647	neutral	None	None	None	None	N
E/V	0.4755	ambiguous	0.418	ambiguous	-0.015	Destabilizing	0.01	N	0.358	neutral	N	0.467532693	None	None	N
E/W	0.9852	likely_pathogenic	0.9802	pathogenic	0.344	Stabilizing	0.999	D	0.726	prob.delet.	None	None	None	None	N
E/Y	0.8832	likely_pathogenic	0.8619	pathogenic	0.31	Stabilizing	0.99	D	0.717	prob.delet.	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.