TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21839	65740;65741;65742	chr2:178583667;178583666;178583665	chr2:179448394;179448393;179448392
N2AB	20198	60817;60818;60819	chr2:178583667;178583666;178583665	chr2:179448394;179448393;179448392
N2A	19271	58036;58037;58038	chr2:178583667;178583666;178583665	chr2:179448394;179448393;179448392
N2B	12774	38545;38546;38547	chr2:178583667;178583666;178583665	chr2:179448394;179448393;179448392
Novex-1	12899	38920;38921;38922	chr2:178583667;178583666;178583665	chr2:179448394;179448393;179448392
Novex-2	12966	39121;39122;39123	chr2:178583667;178583666;178583665	chr2:179448394;179448393;179448392
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCG
• RefSeq wild type template codon: CGC
• Domain: Fn3-46
• Domain position: 83
• Structural Position: 113
• Q(SASA): 0.5612
• 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
A/E	None	None	0.976	N	0.549	0.37	0.573444017615	gnomAD-4.0.0	1.36988E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.80006E-06	0	0
A/T	rs56378177	-0.315	0.929	N	0.505	0.193	None	gnomAD-2.1.1	6.82E-05	None	None	None	None	I	None	1.66099E-04	2.84E-05	None	0	2.6058E-04	None	1.97628E-04	None	0	2.35E-05	0
A/T	rs56378177	-0.315	0.929	N	0.505	0.193	None	gnomAD-3.1.2	8.55E-05	None	None	None	None	I	None	2.17192E-04	0	0	0	1.94099E-04	None	0	0	4.41E-05	0	0
A/T	rs56378177	-0.315	0.929	N	0.505	0.193	None	gnomAD-4.0.0	5.64476E-05	None	None	None	None	I	None	1.46714E-04	0	None	0	3.81286E-04	None	0	3.32779E-04	3.73182E-05	1.32109E-04	8.01667E-05
A/V	rs55948748	-0.036	0.159	N	0.315	0.119	None	gnomAD-2.1.1	4.4563E-03	None	None	None	None	I	None	4.36986E-02	2.84447E-03	None	1.74825E-03	0	None	3.29E-05	None	4.01E-05	4.23842E-04	2.12344E-03
A/V	rs55948748	-0.036	0.159	N	0.315	0.119	None	gnomAD-3.1.2	1.22502E-02	None	None	None	None	I	None	4.16848E-02	5.37634E-03	0	1.7301E-03	0	None	0	0	3.97106E-04	0	1.00575E-02
A/V	rs55948748	-0.036	0.159	N	0.315	0.119	None	1000 genomes	1.41773E-02	None	None	None	None	I	None	5.07E-02	4.3E-03	None	None	0	1E-03	None	None	None	0	None
A/V	rs55948748	-0.036	0.159	N	0.315	0.119	None	gnomAD-4.0.0	2.49612E-03	None	None	None	None	I	None	4.33646E-02	3.62258E-03	None	1.59096E-03	0	None	0	3.32557E-03	2.46808E-04	4.40315E-05	3.1257E-03

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
A/C	0.8079	likely_pathogenic	0.7466	pathogenic	-0.766	Destabilizing	0.998	D	0.561	neutral	None	None	None	None	I
A/D	0.8956	likely_pathogenic	0.8035	pathogenic	-0.336	Destabilizing	0.956	D	0.641	neutral	None	None	None	None	I
A/E	0.8284	likely_pathogenic	0.746	pathogenic	-0.49	Destabilizing	0.976	D	0.549	neutral	N	0.510534109	None	None	I
A/F	0.7693	likely_pathogenic	0.6773	pathogenic	-0.887	Destabilizing	0.956	D	0.651	neutral	None	None	None	None	I
A/G	0.422	ambiguous	0.3271	benign	-0.335	Destabilizing	0.855	D	0.455	neutral	N	0.471450328	None	None	I
A/H	0.8836	likely_pathogenic	0.8193	pathogenic	-0.377	Destabilizing	0.998	D	0.635	neutral	None	None	None	None	I
A/I	0.5903	likely_pathogenic	0.4692	ambiguous	-0.346	Destabilizing	0.787	D	0.552	neutral	None	None	None	None	I
A/K	0.9027	likely_pathogenic	0.8391	pathogenic	-0.588	Destabilizing	0.956	D	0.548	neutral	None	None	None	None	I
A/L	0.4382	ambiguous	0.3571	ambiguous	-0.346	Destabilizing	0.754	D	0.507	neutral	None	None	None	None	I
A/M	0.5245	ambiguous	0.4125	ambiguous	-0.379	Destabilizing	0.988	D	0.572	neutral	None	None	None	None	I
A/N	0.7151	likely_pathogenic	0.5989	pathogenic	-0.267	Destabilizing	0.956	D	0.633	neutral	None	None	None	None	I
A/P	0.6301	likely_pathogenic	0.4931	ambiguous	-0.292	Destabilizing	0.988	D	0.579	neutral	N	0.475207126	None	None	I
A/Q	0.7583	likely_pathogenic	0.6803	pathogenic	-0.543	Destabilizing	0.978	D	0.595	neutral	None	None	None	None	I
A/R	0.8196	likely_pathogenic	0.7524	pathogenic	-0.146	Destabilizing	0.956	D	0.593	neutral	None	None	None	None	I
A/S	0.1928	likely_benign	0.1588	benign	-0.492	Destabilizing	0.267	N	0.299	neutral	N	0.498759677	None	None	I
A/T	0.2615	likely_benign	0.1972	benign	-0.564	Destabilizing	0.929	D	0.505	neutral	N	0.473406246	None	None	I
A/V	0.3009	likely_benign	0.3051	benign	-0.292	Destabilizing	0.159	N	0.315	neutral	N	0.470977164	None	None	I
A/W	0.9514	likely_pathogenic	0.9238	pathogenic	-1.019	Destabilizing	0.998	D	0.722	prob.delet.	None	None	None	None	I
A/Y	0.8788	likely_pathogenic	0.81	pathogenic	-0.67	Destabilizing	0.978	D	0.652	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.