TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16473	49642;49643;49644	chr2:178613866;178613865;178613864	chr2:179478593;179478592;179478591
N2AB	14832	44719;44720;44721	chr2:178613866;178613865;178613864	chr2:179478593;179478592;179478591
N2A	13905	41938;41939;41940	chr2:178613866;178613865;178613864	chr2:179478593;179478592;179478591
N2B	7408	22447;22448;22449	chr2:178613866;178613865;178613864	chr2:179478593;179478592;179478591
Novex-1	7533	22822;22823;22824	chr2:178613866;178613865;178613864	chr2:179478593;179478592;179478591
Novex-2	7600	23023;23024;23025	chr2:178613866;178613865;178613864	chr2:179478593;179478592;179478591
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: Fn3-7
• Domain position: 24
• Structural Position: 26
• Q(SASA): 0.638
• 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/K	rs1422077520	0.314	0.999	N	0.599	0.459	0.37262878642	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	2.91E-05	None	0	0	None	0	None	0	0	0
E/K	rs1422077520	0.314	0.999	N	0.599	0.459	0.37262878642	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	rs1422077520	0.314	0.999	N	0.599	0.459	0.37262878642	gnomAD-4.0.0	2.56785E-06	None	None	None	None	N	None	0	1.69918E-05	None	0	0	None	0	0	2.39796E-06	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	0.2415	likely_benign	0.2622	benign	-0.369	Destabilizing	0.999	D	0.729	prob.delet.	N	0.444622992	None	None	N
E/C	0.9012	likely_pathogenic	0.9184	pathogenic	-0.375	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
E/D	0.3931	ambiguous	0.377	ambiguous	-1.135	Destabilizing	0.999	D	0.524	neutral	N	0.474985199	None	None	N
E/F	0.8917	likely_pathogenic	0.9086	pathogenic	0.331	Stabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
E/G	0.4402	ambiguous	0.4855	ambiguous	-0.733	Destabilizing	1.0	D	0.75	deleterious	N	0.480829483	None	None	N
E/H	0.7452	likely_pathogenic	0.7787	pathogenic	0.262	Stabilizing	1.0	D	0.666	neutral	None	None	None	None	N
E/I	0.4675	ambiguous	0.5212	ambiguous	0.615	Stabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
E/K	0.1983	likely_benign	0.2683	benign	-0.329	Destabilizing	0.999	D	0.599	neutral	N	0.448251386	None	None	N
E/L	0.5197	ambiguous	0.5412	ambiguous	0.615	Stabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
E/M	0.6025	likely_pathogenic	0.6386	pathogenic	0.756	Stabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
E/N	0.6304	likely_pathogenic	0.6565	pathogenic	-0.915	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
E/P	0.4279	ambiguous	0.4345	ambiguous	0.309	Stabilizing	1.0	D	0.782	deleterious	None	None	None	None	N
E/Q	0.2055	likely_benign	0.2312	benign	-0.731	Destabilizing	1.0	D	0.648	neutral	N	0.472163366	None	None	N
E/R	0.366	ambiguous	0.4432	ambiguous	0.045	Stabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
E/S	0.4229	ambiguous	0.4539	ambiguous	-1.151	Destabilizing	0.999	D	0.647	neutral	None	None	None	None	N
E/T	0.4207	ambiguous	0.4575	ambiguous	-0.837	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
E/V	0.3005	likely_benign	0.3505	ambiguous	0.309	Stabilizing	1.0	D	0.783	deleterious	N	0.48023221	None	None	N
E/W	0.9758	likely_pathogenic	0.9808	pathogenic	0.546	Stabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
E/Y	0.83	likely_pathogenic	0.8584	pathogenic	0.584	Stabilizing	1.0	D	0.775	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.