TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24654	74185;74186;74187	chr2:178572172;178572171;178572170	chr2:179436899;179436898;179436897
N2AB	23013	69262;69263;69264	chr2:178572172;178572171;178572170	chr2:179436899;179436898;179436897
N2A	22086	66481;66482;66483	chr2:178572172;178572171;178572170	chr2:179436899;179436898;179436897
N2B	15589	46990;46991;46992	chr2:178572172;178572171;178572170	chr2:179436899;179436898;179436897
Novex-1	15714	47365;47366;47367	chr2:178572172;178572171;178572170	chr2:179436899;179436898;179436897
Novex-2	15781	47566;47567;47568	chr2:178572172;178572171;178572170	chr2:179436899;179436898;179436897
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: Fn3-67
• Domain position: 39
• Structural Position: 41
• Q(SASA): 0.0956
• 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/Q	rs766830917	-1.828	1.0	N	0.745	0.436	0.351180957027	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.94E-06	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	0.8083	likely_pathogenic	0.794	pathogenic	-2.238	Highly Destabilizing	1.0	D	0.691	prob.neutral	D	0.529430986	None	None	N
E/C	0.9878	likely_pathogenic	0.9864	pathogenic	-1.265	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	N
E/D	0.7678	likely_pathogenic	0.7327	pathogenic	-1.63	Destabilizing	0.998	D	0.639	neutral	N	0.492982213	None	None	N
E/F	0.9945	likely_pathogenic	0.9933	pathogenic	-1.969	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
E/G	0.8988	likely_pathogenic	0.8858	pathogenic	-2.605	Highly Destabilizing	1.0	D	0.766	deleterious	D	0.537953362	None	None	N
E/H	0.9565	likely_pathogenic	0.9538	pathogenic	-1.774	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
E/I	0.982	likely_pathogenic	0.9793	pathogenic	-1.171	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
E/K	0.9281	likely_pathogenic	0.9238	pathogenic	-2.006	Highly Destabilizing	1.0	D	0.678	prob.neutral	N	0.504134254	None	None	N
E/L	0.9774	likely_pathogenic	0.9731	pathogenic	-1.171	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
E/M	0.96	likely_pathogenic	0.9537	pathogenic	-0.341	Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
E/N	0.9418	likely_pathogenic	0.9335	pathogenic	-2.071	Highly Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
E/P	0.9998	likely_pathogenic	0.9997	pathogenic	-1.516	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
E/Q	0.4901	ambiguous	0.4723	ambiguous	-1.83	Destabilizing	1.0	D	0.745	deleterious	N	0.469722943	None	None	N
E/R	0.9516	likely_pathogenic	0.9473	pathogenic	-1.722	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
E/S	0.8086	likely_pathogenic	0.7948	pathogenic	-2.833	Highly Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
E/T	0.929	likely_pathogenic	0.9203	pathogenic	-2.481	Highly Destabilizing	1.0	D	0.778	deleterious	None	None	None	None	N
E/V	0.9421	likely_pathogenic	0.9364	pathogenic	-1.516	Destabilizing	1.0	D	0.767	deleterious	D	0.525583099	None	None	N
E/W	0.9972	likely_pathogenic	0.9966	pathogenic	-1.944	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
E/Y	0.9898	likely_pathogenic	0.9877	pathogenic	-1.78	Destabilizing	1.0	D	0.803	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.