TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35734	107425;107426;107427	chr2:178528551;178528550;178528549	chr2:179393278;179393277;179393276
N2AB	34093	102502;102503;102504	chr2:178528551;178528550;178528549	chr2:179393278;179393277;179393276
N2A	33166	99721;99722;99723	chr2:178528551;178528550;178528549	chr2:179393278;179393277;179393276
N2B	26669	80230;80231;80232	chr2:178528551;178528550;178528549	chr2:179393278;179393277;179393276
Novex-1	26794	80605;80606;80607	chr2:178528551;178528550;178528549	chr2:179393278;179393277;179393276
Novex-2	26861	80806;80807;80808	chr2:178528551;178528550;178528549	chr2:179393278;179393277;179393276
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-168
• Domain position: 33
• Structural Position: 47
• Q(SASA): 0.378
• 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	rs374992991	-0.513	0.996	N	0.514	0.336	None	gnomAD-2.1.1	8.16E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.8E-05	0
E/K	rs374992991	-0.513	0.996	N	0.514	0.336	None	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	1.47E-05	0	0
E/K	rs374992991	-0.513	0.996	N	0.514	0.336	None	gnomAD-4.0.0	1.11887E-05	None	None	None	None	N	None	1.33858E-05	0	None	0	2.23294E-05	None	0	0	7.64783E-06	6.63394E-05	1.60637E-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
E/A	0.3822	ambiguous	0.3489	ambiguous	-0.398	Destabilizing	0.955	D	0.555	neutral	N	0.493829152	None	None	N
E/C	0.9699	likely_pathogenic	0.9616	pathogenic	-0.391	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
E/D	0.4416	ambiguous	0.427	ambiguous	-0.916	Destabilizing	0.977	D	0.475	neutral	N	0.5148205	None	None	N
E/F	0.9376	likely_pathogenic	0.9233	pathogenic	0.393	Stabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	N
E/G	0.5716	likely_pathogenic	0.5149	ambiguous	-0.764	Destabilizing	0.955	D	0.637	neutral	N	0.519650317	None	None	N
E/H	0.8106	likely_pathogenic	0.7749	pathogenic	0.4	Stabilizing	1.0	D	0.68	prob.neutral	None	None	None	None	N
E/I	0.6329	likely_pathogenic	0.5939	pathogenic	0.599	Stabilizing	0.998	D	0.735	prob.delet.	None	None	None	None	N
E/K	0.4493	ambiguous	0.384	ambiguous	-0.284	Destabilizing	0.996	D	0.514	neutral	N	0.444016408	None	None	N
E/L	0.7408	likely_pathogenic	0.7099	pathogenic	0.599	Stabilizing	0.995	D	0.677	prob.neutral	None	None	None	None	N
E/M	0.7316	likely_pathogenic	0.7093	pathogenic	0.711	Stabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
E/N	0.6739	likely_pathogenic	0.6412	pathogenic	-0.95	Destabilizing	0.995	D	0.645	neutral	None	None	None	None	N
E/P	0.9948	likely_pathogenic	0.9943	pathogenic	0.288	Stabilizing	0.998	D	0.712	prob.delet.	None	None	None	None	N
E/Q	0.2584	likely_benign	0.2326	benign	-0.775	Destabilizing	0.999	D	0.633	neutral	N	0.419755468	None	None	N
E/R	0.626	likely_pathogenic	0.5601	ambiguous	0.132	Stabilizing	0.995	D	0.678	prob.neutral	None	None	None	None	N
E/S	0.4293	ambiguous	0.4021	ambiguous	-1.196	Destabilizing	0.43	N	0.431	neutral	None	None	None	None	N
E/T	0.4331	ambiguous	0.3975	ambiguous	-0.88	Destabilizing	0.966	D	0.628	neutral	None	None	None	None	N
E/V	0.4449	ambiguous	0.4146	ambiguous	0.288	Stabilizing	0.993	D	0.685	prob.neutral	N	0.473877955	None	None	N
E/W	0.9849	likely_pathogenic	0.9799	pathogenic	0.647	Stabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
E/Y	0.9065	likely_pathogenic	0.8818	pathogenic	0.66	Stabilizing	0.999	D	0.731	prob.delet.	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.