TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4620	14083;14084;14085	chr2:178739375;178739374;178739373	chr2:179604102;179604101;179604100
N2AB	4303	13132;13133;13134	chr2:178739375;178739374;178739373	chr2:179604102;179604101;179604100
N2A	None	None	chr2:None	chr2:None
N2B	4257	12994;12995;12996	chr2:178739375;178739374;178739373	chr2:179604102;179604101;179604100
Novex-1	4382	13369;13370;13371	chr2:178739375;178739374;178739373	chr2:179604102;179604101;179604100
Novex-2	4449	13570;13571;13572	chr2:178739375;178739374;178739373	chr2:179604102;179604101;179604100
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGT
• RefSeq wild type template codon: CCA
• Domain: Ig-29
• Domain position: 15
• Structural Position: 24
• Q(SASA): 0.2882
• 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
G/D	rs55857742	-1.448	0.002	D	0.334	0.404	None	gnomAD-2.1.1	3.5296E-03	None	None	None	None	N	None	2.06594E-04	7.63964E-04	None	1.06465E-03	1.02648E-04	None	2.23842E-02	None	4E-05	1.83849E-03	3.09249E-03
G/D	rs55857742	-1.448	0.002	D	0.334	0.404	None	gnomAD-3.1.2	1.81364E-03	None	None	None	None	N	None	2.41289E-04	1.83366E-03	0	8.65052E-04	0	None	9.41E-05	0	1.69028E-03	2.38391E-02	1.91022E-03
G/D	rs55857742	-1.448	0.002	D	0.334	0.404	None	1000 genomes	5.99042E-03	None	None	None	None	N	None	0	1.4E-03	None	None	0	3E-03	None	None	None	2.66E-02	None
G/D	rs55857742	-1.448	0.002	D	0.334	0.404	None	gnomAD-4.0.0	2.23065E-03	None	None	None	None	N	None	3.19812E-04	9.999E-04	None	8.44652E-04	1.56069E-04	None	7.80982E-05	4.12541E-03	1.10271E-03	2.16298E-02	2.92875E-03
G/R	rs905994651	None	0.81	D	0.669	0.606	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
G/R	rs905994651	None	0.81	D	0.669	0.606	None	gnomAD-4.0.0	6.57168E-06	None	None	None	None	N	None	2.41313E-05	0	None	0	0	None	0	0	0	0	0
G/S	None	None	0.379	D	0.413	0.521	None	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	3.66327E-05
G/V	rs55857742	-0.549	0.81	D	0.701	0.642	None	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	5.58E-05	None	0	None	0	0	0
G/V	rs55857742	-0.549	0.81	D	0.701	0.642	None	gnomAD-4.0.0	1.36838E-06	None	None	None	None	N	None	0	0	None	0	2.52067E-05	None	0	0	8.99444E-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
G/A	0.2512	likely_benign	0.267	benign	-0.553	Destabilizing	0.549	D	0.377	neutral	D	0.758472485	None	None	N
G/C	0.3877	ambiguous	0.4035	ambiguous	-0.967	Destabilizing	0.99	D	0.734	prob.delet.	D	0.757969104	None	None	N
G/D	0.1671	likely_benign	0.2632	benign	-0.975	Destabilizing	0.002	N	0.334	neutral	D	0.602686106	None	None	N
G/E	0.2441	likely_benign	0.2611	benign	-1.133	Destabilizing	0.005	N	0.458	neutral	None	None	None	None	N
G/F	0.6948	likely_pathogenic	0.7168	pathogenic	-1.174	Destabilizing	0.739	D	0.712	prob.delet.	None	None	None	None	N
G/H	0.5107	ambiguous	0.5272	ambiguous	-0.761	Destabilizing	0.012	N	0.551	neutral	None	None	None	None	N
G/I	0.6075	likely_pathogenic	0.6293	pathogenic	-0.612	Destabilizing	0.92	D	0.72	prob.delet.	None	None	None	None	N
G/K	0.4728	ambiguous	0.493	ambiguous	-1.109	Destabilizing	0.447	N	0.649	neutral	None	None	None	None	N
G/L	0.6164	likely_pathogenic	0.6363	pathogenic	-0.612	Destabilizing	0.85	D	0.703	prob.neutral	None	None	None	None	N
G/M	0.6216	likely_pathogenic	0.6336	pathogenic	-0.488	Destabilizing	0.992	D	0.729	prob.delet.	None	None	None	None	N
G/N	0.2365	likely_benign	0.2439	benign	-0.747	Destabilizing	0.447	N	0.46	neutral	None	None	None	None	N
G/P	0.9612	likely_pathogenic	0.969	pathogenic	-0.558	Destabilizing	0.92	D	0.675	neutral	None	None	None	None	N
G/Q	0.4395	ambiguous	0.4621	ambiguous	-1.082	Destabilizing	0.739	D	0.655	neutral	None	None	None	None	N
G/R	0.3966	ambiguous	0.4262	ambiguous	-0.562	Destabilizing	0.81	D	0.669	neutral	D	0.672866288	None	None	N
G/S	0.16	likely_benign	0.17	benign	-0.896	Destabilizing	0.379	N	0.413	neutral	D	0.635071716	None	None	N
G/T	0.3223	likely_benign	0.3337	benign	-0.994	Destabilizing	0.85	D	0.657	neutral	None	None	None	None	N
G/V	0.4708	ambiguous	0.5049	ambiguous	-0.558	Destabilizing	0.81	D	0.701	prob.neutral	D	0.758206865	None	None	N
G/W	0.4785	ambiguous	0.5033	ambiguous	-1.31	Destabilizing	0.977	D	0.705	prob.neutral	None	None	None	None	N
G/Y	0.4947	ambiguous	0.51	ambiguous	-0.993	Destabilizing	0.012	N	0.546	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.