TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13821	41686;41687;41688	chr2:178636110;178636109;178636108	chr2:179500837;179500836;179500835
N2AB	12180	36763;36764;36765	chr2:178636110;178636109;178636108	chr2:179500837;179500836;179500835
N2A	11253	33982;33983;33984	chr2:178636110;178636109;178636108	chr2:179500837;179500836;179500835
N2B	4756	14491;14492;14493	chr2:178636110;178636109;178636108	chr2:179500837;179500836;179500835
Novex-1	4881	14866;14867;14868	chr2:178636110;178636109;178636108	chr2:179500837;179500836;179500835
Novex-2	4948	15067;15068;15069	chr2:178636110;178636109;178636108	chr2:179500837;179500836;179500835
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-88
• Domain position: 42
• Structural Position: 70
• Q(SASA): 0.6013
• 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	rs749586891	-0.005	0.01	N	0.166	0.136	0.117506650769	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	5.63E-05	None	0	None	0	0	0
E/Q	rs749586891	-0.441	0.065	N	0.217	0.073	0.0716867268079	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/Q	rs749586891	-0.441	0.065	N	0.217	0.073	0.0716867268079	gnomAD-4.0.0	1.5925E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.4334E-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	0.288	likely_benign	0.3047	benign	-0.384	Destabilizing	0.006	N	0.262	neutral	N	0.341379391	None	None	N
E/C	0.9533	likely_pathogenic	0.9525	pathogenic	-0.371	Destabilizing	0.995	D	0.261	neutral	None	None	None	None	N
E/D	0.2688	likely_benign	0.289	benign	-0.659	Destabilizing	0.006	N	0.163	neutral	N	0.347271954	None	None	N
E/F	0.9525	likely_pathogenic	0.9564	pathogenic	0.129	Stabilizing	0.944	D	0.349	neutral	None	None	None	None	N
E/G	0.2853	likely_benign	0.2893	benign	-0.671	Destabilizing	0.27	N	0.384	neutral	N	0.344335029	None	None	N
E/H	0.8165	likely_pathogenic	0.8191	pathogenic	0.309	Stabilizing	0.944	D	0.329	neutral	None	None	None	None	N
E/I	0.7485	likely_pathogenic	0.7726	pathogenic	0.368	Stabilizing	0.069	N	0.315	neutral	None	None	None	None	N
E/K	0.4154	ambiguous	0.4119	ambiguous	-0.015	Destabilizing	0.01	N	0.166	neutral	N	0.350368244	None	None	N
E/L	0.7204	likely_pathogenic	0.7527	pathogenic	0.368	Stabilizing	0.329	N	0.349	neutral	None	None	None	None	N
E/M	0.7636	likely_pathogenic	0.7788	pathogenic	0.325	Stabilizing	0.944	D	0.293	neutral	None	None	None	None	N
E/N	0.5178	ambiguous	0.5494	ambiguous	-0.613	Destabilizing	0.543	D	0.209	neutral	None	None	None	None	N
E/P	0.6093	likely_pathogenic	0.6147	pathogenic	0.138	Stabilizing	0.828	D	0.383	neutral	None	None	None	None	N
E/Q	0.2724	likely_benign	0.2724	benign	-0.488	Destabilizing	0.065	N	0.217	neutral	N	0.343922662	None	None	N
E/R	0.6066	likely_pathogenic	0.5805	pathogenic	0.356	Stabilizing	0.543	D	0.213	neutral	None	None	None	None	N
E/S	0.3637	ambiguous	0.3765	ambiguous	-0.763	Destabilizing	0.329	N	0.33	neutral	None	None	None	None	N
E/T	0.471	ambiguous	0.5113	ambiguous	-0.52	Destabilizing	0.031	N	0.259	neutral	None	None	None	None	N
E/V	0.4972	ambiguous	0.5275	ambiguous	0.138	Stabilizing	0.27	N	0.333	neutral	N	0.356963791	None	None	N
E/W	0.9789	likely_pathogenic	0.9778	pathogenic	0.349	Stabilizing	0.995	D	0.311	neutral	None	None	None	None	N
E/Y	0.9064	likely_pathogenic	0.9101	pathogenic	0.379	Stabilizing	0.981	D	0.34	neutral	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.