TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15751	47476;47477;47478	chr2:178618207;178618206;178618205	chr2:179482934;179482933;179482932
N2AB	14110	42553;42554;42555	chr2:178618207;178618206;178618205	chr2:179482934;179482933;179482932
N2A	13183	39772;39773;39774	chr2:178618207;178618206;178618205	chr2:179482934;179482933;179482932
N2B	6686	20281;20282;20283	chr2:178618207;178618206;178618205	chr2:179482934;179482933;179482932
Novex-1	6811	20656;20657;20658	chr2:178618207;178618206;178618205	chr2:179482934;179482933;179482932
Novex-2	6878	20857;20858;20859	chr2:178618207;178618206;178618205	chr2:179482934;179482933;179482932
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: Fn3-1
• Domain position: 95
• Structural Position: 129
• Q(SASA): 0.303
• 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/D	rs764193921	-0.883	0.893	N	0.417	0.082	0.273070737957	gnomAD-2.1.1	8.07E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.79E-05	0
E/D	rs764193921	-0.883	0.893	N	0.417	0.082	0.273070737957	gnomAD-4.0.0	2.05408E-06	None	None	None	None	N	None	2.99491E-05	0	None	0	0	None	0	0	1.79984E-06	0	0
E/K	rs2057702723	None	0.91	N	0.452	0.216	0.222439326576	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/K	rs2057702723	None	0.91	N	0.452	0.216	0.222439326576	gnomAD-4.0.0	6.58241E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.4728E-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	0.1958	likely_benign	0.1551	benign	-0.726	Destabilizing	0.953	D	0.51	neutral	N	0.46176475	None	None	N
E/C	0.907	likely_pathogenic	0.8012	pathogenic	-0.27	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
E/D	0.3437	ambiguous	0.2715	benign	-0.871	Destabilizing	0.893	D	0.417	neutral	N	0.469644738	None	None	N
E/F	0.7888	likely_pathogenic	0.6733	pathogenic	-0.393	Destabilizing	0.998	D	0.853	deleterious	None	None	None	None	N
E/G	0.362	ambiguous	0.3038	benign	-1.029	Destabilizing	0.976	D	0.648	neutral	N	0.490812267	None	None	N
E/H	0.7011	likely_pathogenic	0.5667	pathogenic	-0.579	Destabilizing	0.995	D	0.68	prob.neutral	None	None	None	None	N
E/I	0.3766	ambiguous	0.2861	benign	0.077	Stabilizing	0.998	D	0.863	deleterious	None	None	None	None	N
E/K	0.2792	likely_benign	0.2181	benign	-0.152	Destabilizing	0.91	D	0.452	neutral	N	0.452282025	None	None	N
E/L	0.4211	ambiguous	0.3121	benign	0.077	Stabilizing	0.99	D	0.701	prob.delet.	None	None	None	None	N
E/M	0.49	ambiguous	0.3905	ambiguous	0.409	Stabilizing	1.0	D	0.822	deleterious	None	None	None	None	N
E/N	0.5429	ambiguous	0.4285	ambiguous	-0.58	Destabilizing	0.995	D	0.588	neutral	None	None	None	None	N
E/P	0.6375	likely_pathogenic	0.4576	ambiguous	-0.169	Destabilizing	0.998	D	0.662	prob.neutral	None	None	None	None	N
E/Q	0.1904	likely_benign	0.1515	benign	-0.509	Destabilizing	0.441	N	0.219	neutral	N	0.462115765	None	None	N
E/R	0.4165	ambiguous	0.3266	benign	0.03	Stabilizing	0.964	D	0.581	neutral	None	None	None	None	N
E/S	0.3698	ambiguous	0.2732	benign	-0.817	Destabilizing	0.964	D	0.452	neutral	None	None	None	None	N
E/T	0.3072	likely_benign	0.2293	benign	-0.565	Destabilizing	0.982	D	0.642	neutral	None	None	None	None	N
E/V	0.2208	likely_benign	0.1732	benign	-0.169	Destabilizing	0.993	D	0.625	neutral	N	0.382534542	None	None	N
E/W	0.9425	likely_pathogenic	0.8924	pathogenic	-0.16	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
E/Y	0.7635	likely_pathogenic	0.6236	pathogenic	-0.127	Destabilizing	0.998	D	0.865	deleterious	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.