TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28399	85420;85421;85422	chr2:178560937;178560936;178560935	chr2:179425664;179425663;179425662
N2AB	26758	80497;80498;80499	chr2:178560937;178560936;178560935	chr2:179425664;179425663;179425662
N2A	25831	77716;77717;77718	chr2:178560937;178560936;178560935	chr2:179425664;179425663;179425662
N2B	19334	58225;58226;58227	chr2:178560937;178560936;178560935	chr2:179425664;179425663;179425662
Novex-1	19459	58600;58601;58602	chr2:178560937;178560936;178560935	chr2:179425664;179425663;179425662
Novex-2	19526	58801;58802;58803	chr2:178560937;178560936;178560935	chr2:179425664;179425663;179425662
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: Ig-143
• Domain position: 42
• Structural Position: 69
• Q(SASA): 0.8484
• 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/K	rs397517732	0.551	0.067	N	0.341	0.235	0.333906830038	gnomAD-2.1.1	1.21E-05	None	None	None	None	I	None	6.46E-05	0	None	0	0	None	0	None	0	1.78E-05	0
E/K	rs397517732	0.551	0.067	N	0.341	0.235	0.333906830038	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/K	rs397517732	0.551	0.067	N	0.341	0.235	0.333906830038	gnomAD-4.0.0	2.85058E-05	None	None	None	None	I	None	2.66916E-05	0	None	0	0	None	0	0	3.64464E-05	0	1.60102E-05

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	0.1647	likely_benign	0.1523	benign	-0.176	Destabilizing	0.919	D	0.59	neutral	N	0.510393328	None	None	I
E/C	0.8207	likely_pathogenic	0.8034	pathogenic	-0.234	Destabilizing	1.0	D	0.68	prob.neutral	None	None	None	None	I
E/D	0.1515	likely_benign	0.15	benign	-0.3	Destabilizing	0.958	D	0.467	neutral	N	0.461159373	None	None	I
E/F	0.7564	likely_pathogenic	0.7253	pathogenic	-0.112	Destabilizing	1.0	D	0.659	neutral	None	None	None	None	I
E/G	0.1589	likely_benign	0.1446	benign	-0.337	Destabilizing	0.988	D	0.546	neutral	D	0.53423298	None	None	I
E/H	0.4603	ambiguous	0.4228	ambiguous	0.38	Stabilizing	0.999	D	0.606	neutral	None	None	None	None	I
E/I	0.3688	ambiguous	0.3453	ambiguous	0.203	Stabilizing	0.995	D	0.679	prob.neutral	None	None	None	None	I
E/K	0.1299	likely_benign	0.1128	benign	0.255	Stabilizing	0.067	N	0.341	neutral	N	0.486996394	None	None	I
E/L	0.3878	ambiguous	0.3561	ambiguous	0.203	Stabilizing	0.991	D	0.653	neutral	None	None	None	None	I
E/M	0.4608	ambiguous	0.4293	ambiguous	0.022	Stabilizing	1.0	D	0.612	neutral	None	None	None	None	I
E/N	0.3015	likely_benign	0.2845	benign	0.017	Stabilizing	0.991	D	0.6	neutral	None	None	None	None	I
E/P	0.4165	ambiguous	0.3776	ambiguous	0.096	Stabilizing	0.995	D	0.639	neutral	None	None	None	None	I
E/Q	0.138	likely_benign	0.1317	benign	0.039	Stabilizing	0.958	D	0.521	neutral	D	0.535886419	None	None	I
E/R	0.2181	likely_benign	0.1926	benign	0.556	Stabilizing	0.982	D	0.578	neutral	None	None	None	None	I
E/S	0.2076	likely_benign	0.1946	benign	-0.156	Destabilizing	0.968	D	0.572	neutral	None	None	None	None	I
E/T	0.2028	likely_benign	0.1963	benign	-0.025	Destabilizing	0.991	D	0.598	neutral	None	None	None	None	I
E/V	0.2123	likely_benign	0.1962	benign	0.096	Stabilizing	0.988	D	0.629	neutral	D	0.534675697	None	None	I
E/W	0.8787	likely_pathogenic	0.8493	pathogenic	-0.017	Destabilizing	1.0	D	0.682	prob.neutral	None	None	None	None	I
E/Y	0.6594	likely_pathogenic	0.6168	pathogenic	0.117	Stabilizing	0.998	D	0.635	neutral	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.