TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15068	45427;45428;45429	chr2:178621622;178621621;178621620	chr2:179486349;179486348;179486347
N2AB	13427	40504;40505;40506	chr2:178621622;178621621;178621620	chr2:179486349;179486348;179486347
N2A	12500	37723;37724;37725	chr2:178621622;178621621;178621620	chr2:179486349;179486348;179486347
N2B	6003	18232;18233;18234	chr2:178621622;178621621;178621620	chr2:179486349;179486348;179486347
Novex-1	6128	18607;18608;18609	chr2:178621622;178621621;178621620	chr2:179486349;179486348;179486347
Novex-2	6195	18808;18809;18810	chr2:178621622;178621621;178621620	chr2:179486349;179486348;179486347
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-102
• Domain position: 38
• Structural Position: 55
• Q(SASA): 0.6324
• 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	rs2058292632	None	0.565	N	0.499	0.252	0.384419519794	gnomAD-3.1.2	6.59E-06	None	None	None	None	N	None	2.42E-05	0	0	0	0	None	0	0	0	0	0
E/K	rs2058292632	None	0.565	N	0.499	0.252	0.384419519794	gnomAD-4.0.0	1.55046E-05	None	None	None	None	N	None	4.01102E-05	0	None	0	0	None	0	0	1.86579E-05	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	0.1725	likely_benign	0.1546	benign	-0.371	Destabilizing	0.565	D	0.475	neutral	N	0.510046502	None	None	N
E/C	0.8553	likely_pathogenic	0.8552	pathogenic	-0.25	Destabilizing	0.996	D	0.563	neutral	None	None	None	None	N
E/D	0.1419	likely_benign	0.1345	benign	-0.395	Destabilizing	0.008	N	0.211	neutral	D	0.542818331	None	None	N
E/F	0.7554	likely_pathogenic	0.7285	pathogenic	-0.156	Destabilizing	0.961	D	0.54	neutral	None	None	None	None	N
E/G	0.2023	likely_benign	0.1798	benign	-0.572	Destabilizing	0.722	D	0.484	neutral	D	0.557152062	None	None	N
E/H	0.4492	ambiguous	0.4158	ambiguous	0.216	Stabilizing	0.961	D	0.421	neutral	None	None	None	None	N
E/I	0.3313	likely_benign	0.3049	benign	0.127	Stabilizing	0.858	D	0.507	neutral	None	None	None	None	N
E/K	0.1097	likely_benign	0.0887	benign	0.203	Stabilizing	0.565	D	0.499	neutral	N	0.499072437	None	None	N
E/L	0.422	ambiguous	0.4014	ambiguous	0.127	Stabilizing	0.633	D	0.499	neutral	None	None	None	None	N
E/M	0.4199	ambiguous	0.4001	ambiguous	0.076	Stabilizing	0.989	D	0.506	neutral	None	None	None	None	N
E/N	0.2494	likely_benign	0.2123	benign	-0.197	Destabilizing	0.858	D	0.412	neutral	None	None	None	None	N
E/P	0.9227	likely_pathogenic	0.9215	pathogenic	-0.019	Destabilizing	0.961	D	0.471	neutral	None	None	None	None	N
E/Q	0.1346	likely_benign	0.1209	benign	-0.141	Destabilizing	0.092	N	0.241	neutral	N	0.490789755	None	None	N
E/R	0.1972	likely_benign	0.1765	benign	0.512	Stabilizing	0.923	D	0.411	neutral	None	None	None	None	N
E/S	0.2192	likely_benign	0.1938	benign	-0.344	Destabilizing	0.633	D	0.433	neutral	None	None	None	None	N
E/T	0.1937	likely_benign	0.1697	benign	-0.176	Destabilizing	0.775	D	0.469	neutral	None	None	None	None	N
E/V	0.2091	likely_benign	0.1932	benign	-0.019	Destabilizing	0.018	N	0.29	neutral	N	0.510163456	None	None	N
E/W	0.8836	likely_pathogenic	0.8747	pathogenic	0.011	Stabilizing	0.996	D	0.617	neutral	None	None	None	None	N
E/Y	0.6199	likely_pathogenic	0.6067	pathogenic	0.084	Stabilizing	0.987	D	0.514	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.