TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33470	100633;100634;100635	chr2:178536339;178536338;178536337	chr2:179401066;179401065;179401064
N2AB	31829	95710;95711;95712	chr2:178536339;178536338;178536337	chr2:179401066;179401065;179401064
N2A	30902	92929;92930;92931	chr2:178536339;178536338;178536337	chr2:179401066;179401065;179401064
N2B	24405	73438;73439;73440	chr2:178536339;178536338;178536337	chr2:179401066;179401065;179401064
Novex-1	24530	73813;73814;73815	chr2:178536339;178536338;178536337	chr2:179401066;179401065;179401064
Novex-2	24597	74014;74015;74016	chr2:178536339;178536338;178536337	chr2:179401066;179401065;179401064
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: Fn3-131
• Domain position: 79
• Structural Position: 111
• Q(SASA): 0.3614
• 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	None	None	0.999	N	0.489	0.342	0.442977140156	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
E/K	None	None	0.999	N	0.583	0.391	0.3349148499	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.625E-06	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	0.4059	ambiguous	0.3715	ambiguous	-0.902	Destabilizing	0.999	D	0.711	prob.delet.	N	0.499258323	None	None	I
E/C	0.9374	likely_pathogenic	0.9287	pathogenic	-0.733	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	I
E/D	0.5812	likely_pathogenic	0.4925	ambiguous	-1.596	Destabilizing	0.999	D	0.489	neutral	N	0.486510525	None	None	I
E/F	0.9149	likely_pathogenic	0.9041	pathogenic	-0.911	Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	I
E/G	0.5406	ambiguous	0.5126	ambiguous	-1.265	Destabilizing	1.0	D	0.785	deleterious	N	0.486510525	None	None	I
E/H	0.8279	likely_pathogenic	0.8183	pathogenic	-1.227	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	I
E/I	0.5929	likely_pathogenic	0.5507	ambiguous	0.089	Stabilizing	1.0	D	0.897	deleterious	None	None	None	None	I
E/K	0.3807	ambiguous	0.3911	ambiguous	-1.074	Destabilizing	0.999	D	0.583	neutral	N	0.508571239	None	None	I
E/L	0.7704	likely_pathogenic	0.7278	pathogenic	0.089	Stabilizing	1.0	D	0.874	deleterious	None	None	None	None	I
E/M	0.7474	likely_pathogenic	0.7098	pathogenic	0.627	Stabilizing	1.0	D	0.853	deleterious	None	None	None	None	I
E/N	0.7234	likely_pathogenic	0.6548	pathogenic	-1.355	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	I
E/P	0.9944	likely_pathogenic	0.9943	pathogenic	-0.221	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	I
E/Q	0.2524	likely_benign	0.2451	benign	-1.185	Destabilizing	1.0	D	0.644	neutral	N	0.511014112	None	None	I
E/R	0.5362	ambiguous	0.5715	pathogenic	-1.009	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	I
E/S	0.5055	ambiguous	0.4551	ambiguous	-1.825	Destabilizing	0.999	D	0.631	neutral	None	None	None	None	I
E/T	0.5078	ambiguous	0.4658	ambiguous	-1.503	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	I
E/V	0.4203	ambiguous	0.3786	ambiguous	-0.221	Destabilizing	1.0	D	0.839	deleterious	N	0.392007854	None	None	I
E/W	0.9785	likely_pathogenic	0.9785	pathogenic	-0.989	Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	I
E/Y	0.909	likely_pathogenic	0.8987	pathogenic	-0.728	Destabilizing	1.0	D	0.868	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.