TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30095	90508;90509;90510	chr2:178552617;178552616;178552615	chr2:179417344;179417343;179417342
N2AB	28454	85585;85586;85587	chr2:178552617;178552616;178552615	chr2:179417344;179417343;179417342
N2A	27527	82804;82805;82806	chr2:178552617;178552616;178552615	chr2:179417344;179417343;179417342
N2B	21030	63313;63314;63315	chr2:178552617;178552616;178552615	chr2:179417344;179417343;179417342
Novex-1	21155	63688;63689;63690	chr2:178552617;178552616;178552615	chr2:179417344;179417343;179417342
Novex-2	21222	63889;63890;63891	chr2:178552617;178552616;178552615	chr2:179417344;179417343;179417342
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: Fn3-107
• Domain position: 66
• Structural Position: 99
• Q(SASA): 0.5135
• 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/G	rs766497887	-1.194	1.0	N	0.589	0.545	0.587690973971	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
E/G	rs766497887	-1.194	1.0	N	0.589	0.545	0.587690973971	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
E/G	rs766497887	-1.194	1.0	N	0.589	0.545	0.587690973971	gnomAD-4.0.0	5.12357E-06	None	None	None	None	N	None	0	3.38949E-05	None	0	0	None	0	0	4.78535E-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	0.3189	likely_benign	0.2814	benign	-0.707	Destabilizing	0.999	D	0.644	neutral	N	0.475519387	None	None	N
E/C	0.9623	likely_pathogenic	0.9498	pathogenic	-0.252	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	N
E/D	0.3437	ambiguous	0.3271	benign	-0.731	Destabilizing	0.999	D	0.598	neutral	N	0.50095793	None	None	N
E/F	0.9489	likely_pathogenic	0.9312	pathogenic	-0.481	Destabilizing	1.0	D	0.637	neutral	None	None	None	None	N
E/G	0.3584	ambiguous	0.3084	benign	-0.971	Destabilizing	1.0	D	0.589	neutral	N	0.50121142	None	None	N
E/H	0.8735	likely_pathogenic	0.8375	pathogenic	-0.554	Destabilizing	1.0	D	0.623	neutral	None	None	None	None	N
E/I	0.7244	likely_pathogenic	0.6702	pathogenic	-0.018	Destabilizing	1.0	D	0.637	neutral	None	None	None	None	N
E/K	0.5234	ambiguous	0.493	ambiguous	-0.145	Destabilizing	0.999	D	0.682	prob.neutral	N	0.488587667	None	None	N
E/L	0.7743	likely_pathogenic	0.7278	pathogenic	-0.018	Destabilizing	1.0	D	0.621	neutral	None	None	None	None	N
E/M	0.7807	likely_pathogenic	0.7282	pathogenic	0.27	Stabilizing	1.0	D	0.608	neutral	None	None	None	None	N
E/N	0.6114	likely_pathogenic	0.5677	pathogenic	-0.488	Destabilizing	1.0	D	0.653	neutral	None	None	None	None	N
E/P	0.5858	likely_pathogenic	0.56	ambiguous	-0.227	Destabilizing	1.0	D	0.596	neutral	None	None	None	None	N
E/Q	0.305	likely_benign	0.2635	benign	-0.446	Destabilizing	1.0	D	0.661	neutral	N	0.477320267	None	None	N
E/R	0.7078	likely_pathogenic	0.6649	pathogenic	0.067	Stabilizing	1.0	D	0.649	neutral	None	None	None	None	N
E/S	0.4843	ambiguous	0.4378	ambiguous	-0.706	Destabilizing	0.999	D	0.673	neutral	None	None	None	None	N
E/T	0.5556	ambiguous	0.4968	ambiguous	-0.496	Destabilizing	1.0	D	0.623	neutral	None	None	None	None	N
E/V	0.534	ambiguous	0.4756	ambiguous	-0.227	Destabilizing	1.0	D	0.595	neutral	N	0.497995416	None	None	N
E/W	0.9843	likely_pathogenic	0.9784	pathogenic	-0.28	Destabilizing	1.0	D	0.69	prob.neutral	None	None	None	None	N
E/Y	0.8979	likely_pathogenic	0.8717	pathogenic	-0.237	Destabilizing	1.0	D	0.6	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.