TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16740	50443;50444;50445	chr2:178612307;178612306;178612305	chr2:179477034;179477033;179477032
N2AB	15099	45520;45521;45522	chr2:178612307;178612306;178612305	chr2:179477034;179477033;179477032
N2A	14172	42739;42740;42741	chr2:178612307;178612306;178612305	chr2:179477034;179477033;179477032
N2B	7675	23248;23249;23250	chr2:178612307;178612306;178612305	chr2:179477034;179477033;179477032
Novex-1	7800	23623;23624;23625	chr2:178612307;178612306;178612305	chr2:179477034;179477033;179477032
Novex-2	7867	23824;23825;23826	chr2:178612307;178612306;178612305	chr2:179477034;179477033;179477032
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: Fn3-9
• Domain position: 90
• Structural Position: 124
• Q(SASA): 0.8813
• 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
E/G	rs1314963445	-0.056	None	N	0.283	0.106	0.235038932564	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
E/G	rs1314963445	-0.056	None	N	0.283	0.106	0.235038932564	gnomAD-4.0.0	6.57903E-06	None	None	None	None	I	None	2.41441E-05	0	None	0	0	None	0	0	0	0	0
E/K	rs771586396	0.737	0.058	N	0.456	0.115	0.258779203287	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
E/K	rs771586396	0.737	0.058	N	0.456	0.115	0.258779203287	gnomAD-4.0.0	2.05414E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79978E-06	1.16012E-05	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	0.1963	likely_benign	0.1928	benign	-0.028	Destabilizing	0.001	N	0.341	neutral	N	0.469450621	None	None	I
E/C	0.905	likely_pathogenic	0.9052	pathogenic	-0.284	Destabilizing	0.869	D	0.489	neutral	None	None	None	None	I
E/D	0.2243	likely_benign	0.1995	benign	-0.346	Destabilizing	0.058	N	0.481	neutral	N	0.461625683	None	None	I
E/F	0.9032	likely_pathogenic	0.901	pathogenic	-0.079	Destabilizing	0.637	D	0.521	neutral	None	None	None	None	I
E/G	0.1807	likely_benign	0.2012	benign	-0.135	Destabilizing	None	N	0.283	neutral	N	0.470345501	None	None	I
E/H	0.7532	likely_pathogenic	0.728	pathogenic	0.589	Stabilizing	0.869	D	0.358	neutral	None	None	None	None	I
E/I	0.6369	likely_pathogenic	0.6057	pathogenic	0.196	Stabilizing	0.221	N	0.589	neutral	None	None	None	None	I
E/K	0.3313	likely_benign	0.3254	benign	0.341	Stabilizing	0.058	N	0.456	neutral	N	0.471296159	None	None	I
E/L	0.6321	likely_pathogenic	0.6054	pathogenic	0.196	Stabilizing	0.075	N	0.521	neutral	None	None	None	None	I
E/M	0.6693	likely_pathogenic	0.6557	pathogenic	-0.083	Destabilizing	0.869	D	0.504	neutral	None	None	None	None	I
E/N	0.4437	ambiguous	0.421	ambiguous	0.119	Stabilizing	0.075	N	0.443	neutral	None	None	None	None	I
E/P	0.4879	ambiguous	0.4795	ambiguous	0.139	Stabilizing	0.366	N	0.476	neutral	None	None	None	None	I
E/Q	0.26	likely_benign	0.2481	benign	0.12	Stabilizing	0.303	N	0.476	neutral	N	0.496400668	None	None	I
E/R	0.4686	ambiguous	0.4743	ambiguous	0.611	Stabilizing	0.366	N	0.423	neutral	None	None	None	None	I
E/S	0.2474	likely_benign	0.2448	benign	-0.029	Destabilizing	0.039	N	0.392	neutral	None	None	None	None	I
E/T	0.2879	likely_benign	0.2761	benign	0.066	Stabilizing	0.001	N	0.317	neutral	None	None	None	None	I
E/V	0.42	ambiguous	0.3896	ambiguous	0.139	Stabilizing	0.058	N	0.49	neutral	N	0.459626182	None	None	I
E/W	0.9608	likely_pathogenic	0.9625	pathogenic	-0.038	Destabilizing	0.869	D	0.539	neutral	None	None	None	None	I
E/Y	0.859	likely_pathogenic	0.8575	pathogenic	0.143	Stabilizing	0.637	D	0.535	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.