TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17857	53794;53795;53796	chr2:178607033;178607032;178607031	chr2:179471760;179471759;179471758
N2AB	16216	48871;48872;48873	chr2:178607033;178607032;178607031	chr2:179471760;179471759;179471758
N2A	15289	46090;46091;46092	chr2:178607033;178607032;178607031	chr2:179471760;179471759;179471758
N2B	8792	26599;26600;26601	chr2:178607033;178607032;178607031	chr2:179471760;179471759;179471758
Novex-1	8917	26974;26975;26976	chr2:178607033;178607032;178607031	chr2:179471760;179471759;179471758
Novex-2	8984	27175;27176;27177	chr2:178607033;178607032;178607031	chr2:179471760;179471759;179471758
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-17
• Domain position: 94
• Structural Position: 131
• Q(SASA): 0.4909
• 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
V/A	rs1352428551	-0.566	0.236	N	0.215	0.088	0.338834610459	gnomAD-2.1.1	3.19E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	6.49E-05	0
V/A	rs1352428551	-0.566	0.236	N	0.215	0.088	0.338834610459	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
V/A	rs1352428551	-0.566	0.236	N	0.215	0.088	0.338834610459	gnomAD-4.0.0	5.15981E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.60841E-06	0	0
V/F	rs1423994048	-0.864	0.998	N	0.294	0.321	0.721568202884	gnomAD-2.1.1	3.19E-05	None	None	None	None	I	None	1.14811E-04	0	None	0	0	None	0	None	0	0	0
V/F	rs1423994048	-0.864	0.998	N	0.294	0.321	0.721568202884	gnomAD-3.1.2	1.32E-05	None	None	None	None	I	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
V/F	rs1423994048	-0.864	0.998	N	0.294	0.321	0.721568202884	gnomAD-4.0.0	1.86471E-06	None	None	None	None	I	None	4.02555E-05	0	None	0	0	None	0	0	0	0	0
V/I	rs1423994048	-0.251	0.979	N	0.42	0.115	0.360961692134	gnomAD-2.1.1	1.23E-05	None	None	None	None	I	None	0	8.94E-05	None	0	0	None	0	None	0	0	0
V/I	rs1423994048	-0.251	0.979	N	0.42	0.115	0.360961692134	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	6.56E-05	0	0	0	None	0	0	0	0	0
V/I	rs1423994048	-0.251	0.979	N	0.42	0.115	0.360961692134	gnomAD-4.0.0	3.72942E-06	None	None	None	None	I	None	0	1.01826E-04	None	0	0	None	0	0	0	0	0
V/L	None	None	0.905	N	0.411	0.169	0.262662153117	gnomAD-4.0.0	6.86396E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.00589E-07	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
V/A	0.2604	likely_benign	0.3039	benign	-1.408	Destabilizing	0.236	N	0.215	neutral	N	0.445018406	None	None	I
V/C	0.7623	likely_pathogenic	0.8103	pathogenic	-0.945	Destabilizing	1.0	D	0.384	neutral	None	None	None	None	I
V/D	0.761	likely_pathogenic	0.8146	pathogenic	-1.614	Destabilizing	0.976	D	0.596	neutral	N	0.511339399	None	None	I
V/E	0.4348	ambiguous	0.5047	ambiguous	-1.689	Destabilizing	0.486	N	0.35	neutral	None	None	None	None	I
V/F	0.4165	ambiguous	0.4731	ambiguous	-1.445	Destabilizing	0.998	D	0.294	neutral	N	0.472731002	None	None	I
V/G	0.4872	ambiguous	0.5477	ambiguous	-1.627	Destabilizing	0.958	D	0.581	neutral	N	0.469858136	None	None	I
V/H	0.7689	likely_pathogenic	0.8418	pathogenic	-1.131	Destabilizing	1.0	D	0.705	prob.delet.	None	None	None	None	I
V/I	0.0907	likely_benign	0.0965	benign	-0.932	Destabilizing	0.979	D	0.42	neutral	N	0.477976187	None	None	I
V/K	0.3773	ambiguous	0.4889	ambiguous	-1.115	Destabilizing	0.991	D	0.442	neutral	None	None	None	None	I
V/L	0.3292	likely_benign	0.3883	ambiguous	-0.932	Destabilizing	0.905	D	0.411	neutral	N	0.444498331	None	None	I
V/M	0.1865	likely_benign	0.21	benign	-0.576	Destabilizing	0.998	D	0.307	neutral	None	None	None	None	I
V/N	0.5365	ambiguous	0.606	pathogenic	-0.886	Destabilizing	0.995	D	0.727	deleterious	None	None	None	None	I
V/P	0.9773	likely_pathogenic	0.9796	pathogenic	-1.057	Destabilizing	0.995	D	0.645	neutral	None	None	None	None	I
V/Q	0.3363	likely_benign	0.4277	ambiguous	-1.213	Destabilizing	0.991	D	0.647	neutral	None	None	None	None	I
V/R	0.3528	ambiguous	0.4923	ambiguous	-0.443	Destabilizing	0.991	D	0.731	deleterious	None	None	None	None	I
V/S	0.3352	likely_benign	0.4003	ambiguous	-1.272	Destabilizing	0.939	D	0.476	neutral	None	None	None	None	I
V/T	0.2146	likely_benign	0.2529	benign	-1.258	Destabilizing	0.968	D	0.375	neutral	None	None	None	None	I
V/W	0.9454	likely_pathogenic	0.963	pathogenic	-1.536	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	I
V/Y	0.8039	likely_pathogenic	0.8514	pathogenic	-1.265	Destabilizing	0.998	D	0.293	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.