TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16463	49612;49613;49614	chr2:178613896;178613895;178613894	chr2:179478623;179478622;179478621
N2AB	14822	44689;44690;44691	chr2:178613896;178613895;178613894	chr2:179478623;179478622;179478621
N2A	13895	41908;41909;41910	chr2:178613896;178613895;178613894	chr2:179478623;179478622;179478621
N2B	7398	22417;22418;22419	chr2:178613896;178613895;178613894	chr2:179478623;179478622;179478621
Novex-1	7523	22792;22793;22794	chr2:178613896;178613895;178613894	chr2:179478623;179478622;179478621
Novex-2	7590	22993;22994;22995	chr2:178613896;178613895;178613894	chr2:179478623;179478622;179478621
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-7
• Domain position: 14
• Structural Position: 16
• Q(SASA): 0.2565
• 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
T/I	rs541307234	None	0.994	D	0.409	0.49	0.584859779323	gnomAD-4.0.0	6.85616E-07	None	None	None	None	N	None	3.0003E-05	0	None	0	0	None	0	0	0	0	0
T/N	None	-1.133	0.998	N	0.405	0.362	0.396794106654	gnomAD-2.1.1	1.63E-05	None	None	None	None	N	None	0	0	None	0	1.12145E-04	None	6.7E-05	None	0	0	0
T/N	None	-1.133	0.998	N	0.405	0.362	0.396794106654	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	1.95389E-04	None	0	0	0	0	0
T/N	None	-1.133	0.998	N	0.405	0.362	0.396794106654	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	0	None	None	1E-03	0	None	None	None	0	None
T/N	None	-1.133	0.998	N	0.405	0.362	0.396794106654	gnomAD-4.0.0	6.82967E-06	None	None	None	None	N	None	0	0	None	0	4.47407E-05	None	0	0	1.69743E-06	6.63101E-05	1.60406E-05
T/S	rs541307234	-1.327	0.835	N	0.501	0.152	0.18995819373	gnomAD-2.1.1	4.07E-06	None	None	None	None	N	None	6.49E-05	0	None	0	0	None	0	None	0	0	0
T/S	rs541307234	-1.327	0.835	N	0.501	0.152	0.18995819373	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
T/S	rs541307234	-1.327	0.835	N	0.501	0.152	0.18995819373	gnomAD-4.0.0	6.58068E-06	None	None	None	None	N	None	2.41406E-05	0	None	0	0	None	0	0	0	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
T/A	0.2014	likely_benign	0.1654	benign	-0.785	Destabilizing	0.122	N	0.146	neutral	N	0.491029112	None	None	N
T/C	0.6097	likely_pathogenic	0.5476	ambiguous	-0.631	Destabilizing	1.0	D	0.447	neutral	None	None	None	None	N
T/D	0.8141	likely_pathogenic	0.8077	pathogenic	-0.98	Destabilizing	0.996	D	0.411	neutral	None	None	None	None	N
T/E	0.7876	likely_pathogenic	0.7982	pathogenic	-0.932	Destabilizing	0.985	D	0.412	neutral	None	None	None	None	N
T/F	0.6992	likely_pathogenic	0.6537	pathogenic	-0.699	Destabilizing	0.999	D	0.527	neutral	None	None	None	None	N
T/G	0.3635	ambiguous	0.2568	benign	-1.096	Destabilizing	0.942	D	0.454	neutral	None	None	None	None	N
T/H	0.6172	likely_pathogenic	0.5875	pathogenic	-1.393	Destabilizing	1.0	D	0.515	neutral	None	None	None	None	N
T/I	0.7132	likely_pathogenic	0.7214	pathogenic	-0.033	Destabilizing	0.994	D	0.409	neutral	D	0.623560331	None	None	N
T/K	0.6381	likely_pathogenic	0.6722	pathogenic	-0.857	Destabilizing	0.97	D	0.419	neutral	None	None	None	None	N
T/L	0.321	likely_benign	0.2995	benign	-0.033	Destabilizing	0.97	D	0.425	neutral	None	None	None	None	N
T/M	0.2464	likely_benign	0.2424	benign	0.256	Stabilizing	1.0	D	0.446	neutral	None	None	None	None	N
T/N	0.3017	likely_benign	0.3031	benign	-1.035	Destabilizing	0.998	D	0.405	neutral	N	0.484742981	None	None	N
T/P	0.8327	likely_pathogenic	0.8332	pathogenic	-0.25	Destabilizing	0.994	D	0.413	neutral	D	0.639326629	None	None	N
T/Q	0.509	ambiguous	0.4948	ambiguous	-1.155	Destabilizing	0.999	D	0.446	neutral	None	None	None	None	N
T/R	0.5538	ambiguous	0.5948	pathogenic	-0.661	Destabilizing	0.996	D	0.435	neutral	None	None	None	None	N
T/S	0.1765	likely_benign	0.134	benign	-1.221	Destabilizing	0.835	D	0.501	neutral	N	0.474469379	None	None	N
T/V	0.4777	ambiguous	0.4616	ambiguous	-0.25	Destabilizing	0.97	D	0.435	neutral	None	None	None	None	N
T/W	0.9292	likely_pathogenic	0.9203	pathogenic	-0.703	Destabilizing	1.0	D	0.57	neutral	None	None	None	None	N
T/Y	0.7418	likely_pathogenic	0.7194	pathogenic	-0.432	Destabilizing	0.999	D	0.531	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.