TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15669	47230;47231;47232	chr2:178618453;178618452;178618451	chr2:179483180;179483179;179483178
N2AB	14028	42307;42308;42309	chr2:178618453;178618452;178618451	chr2:179483180;179483179;179483178
N2A	13101	39526;39527;39528	chr2:178618453;178618452;178618451	chr2:179483180;179483179;179483178
N2B	6604	20035;20036;20037	chr2:178618453;178618452;178618451	chr2:179483180;179483179;179483178
Novex-1	6729	20410;20411;20412	chr2:178618453;178618452;178618451	chr2:179483180;179483179;179483178
Novex-2	6796	20611;20612;20613	chr2:178618453;178618452;178618451	chr2:179483180;179483179;179483178
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-1
• Domain position: 13
• Structural Position: 15
• Q(SASA): 0.249
• 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	rs773039098	-0.302	0.004	N	0.257	0.158	0.256283259241	gnomAD-2.1.1	8.09E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.79E-05	0
T/I	rs773039098	-0.302	0.004	N	0.257	0.158	0.256283259241	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	6.56E-05	0	0	0	None	0	0	0	0	0
T/I	rs773039098	-0.302	0.004	N	0.257	0.158	0.256283259241	gnomAD-4.0.0	2.60495E-05	None	None	None	None	N	None	0	1.67118E-05	None	0	0	None	0	0	3.39242E-05	0	1.60328E-05

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	0.2027	likely_benign	0.1904	benign	-1.199	Destabilizing	0.002	N	0.241	neutral	N	0.472699668	None	None	N
T/C	0.5596	ambiguous	0.468	ambiguous	-0.867	Destabilizing	0.947	D	0.547	neutral	None	None	None	None	N
T/D	0.8133	likely_pathogenic	0.7832	pathogenic	-0.516	Destabilizing	0.7	D	0.529	neutral	None	None	None	None	N
T/E	0.729	likely_pathogenic	0.645	pathogenic	-0.452	Destabilizing	0.7	D	0.49	neutral	None	None	None	None	N
T/F	0.7017	likely_pathogenic	0.6409	pathogenic	-1.184	Destabilizing	0.7	D	0.659	neutral	None	None	None	None	N
T/G	0.5932	likely_pathogenic	0.5608	ambiguous	-1.491	Destabilizing	0.25	N	0.543	neutral	None	None	None	None	N
T/H	0.6695	likely_pathogenic	0.5978	pathogenic	-1.71	Destabilizing	0.982	D	0.649	neutral	None	None	None	None	N
T/I	0.3008	likely_benign	0.2615	benign	-0.484	Destabilizing	0.004	N	0.257	neutral	N	0.438938206	None	None	N
T/K	0.6273	likely_pathogenic	0.5315	ambiguous	-0.632	Destabilizing	0.638	D	0.489	neutral	N	0.48107748	None	None	N
T/L	0.3008	likely_benign	0.2514	benign	-0.484	Destabilizing	0.121	N	0.492	neutral	None	None	None	None	N
T/M	0.2004	likely_benign	0.176	benign	-0.248	Destabilizing	0.898	D	0.549	neutral	None	None	None	None	N
T/N	0.31	likely_benign	0.3051	benign	-0.748	Destabilizing	0.826	D	0.467	neutral	None	None	None	None	N
T/P	0.5763	likely_pathogenic	0.5069	ambiguous	-0.692	Destabilizing	0.638	D	0.551	neutral	N	0.482225565	None	None	N
T/Q	0.5848	likely_pathogenic	0.4875	ambiguous	-0.878	Destabilizing	0.826	D	0.563	neutral	None	None	None	None	N
T/R	0.5807	likely_pathogenic	0.4882	ambiguous	-0.55	Destabilizing	0.638	D	0.553	neutral	N	0.481364509	None	None	N
T/S	0.2842	likely_benign	0.272	benign	-1.11	Destabilizing	0.201	N	0.471	neutral	N	0.481562195	None	None	N
T/V	0.2122	likely_benign	0.1913	benign	-0.692	Destabilizing	0.121	N	0.506	neutral	None	None	None	None	N
T/W	0.9215	likely_pathogenic	0.8776	pathogenic	-1.071	Destabilizing	0.982	D	0.682	prob.neutral	None	None	None	None	N
T/Y	0.684	likely_pathogenic	0.6106	pathogenic	-0.813	Destabilizing	0.826	D	0.663	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.