TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6727	20404;20405;20406	chr2:178727186;178727185;178727184	chr2:179591913;179591912;179591911
N2AB	6410	19453;19454;19455	chr2:178727186;178727185;178727184	chr2:179591913;179591912;179591911
N2A	5483	16672;16673;16674	chr2:178727186;178727185;178727184	chr2:179591913;179591912;179591911
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: M
• RefSeq wild type transcript codon: ATG
• RefSeq wild type template codon: TAC
• Domain: Ig-51
• Domain position: 61
• Structural Position: 140
• Q(SASA): 0.1342
• 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
M/L	None	None	None	N	0.261	0.226	0.437100570223	gnomAD-4.0.0	1.36888E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79943E-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
M/A	0.7827	likely_pathogenic	0.8483	pathogenic	-2.317	Highly Destabilizing	0.003	N	0.441	neutral	None	None	None	None	N
M/C	0.9236	likely_pathogenic	0.9311	pathogenic	-2.591	Highly Destabilizing	0.995	D	0.729	prob.delet.	None	None	None	None	N
M/D	0.9918	likely_pathogenic	0.9957	pathogenic	-2.114	Highly Destabilizing	0.985	D	0.765	deleterious	None	None	None	None	N
M/E	0.937	likely_pathogenic	0.9653	pathogenic	-1.842	Destabilizing	0.963	D	0.703	prob.neutral	None	None	None	None	N
M/F	0.411	ambiguous	0.4298	ambiguous	-0.781	Destabilizing	0.137	N	0.567	neutral	None	None	None	None	N
M/G	0.9299	likely_pathogenic	0.9528	pathogenic	-2.855	Highly Destabilizing	0.772	D	0.715	prob.delet.	None	None	None	None	N
M/H	0.9396	likely_pathogenic	0.9666	pathogenic	-2.562	Highly Destabilizing	0.999	D	0.795	deleterious	None	None	None	None	N
M/I	0.3699	ambiguous	0.4166	ambiguous	-0.754	Destabilizing	0.001	N	0.267	neutral	N	0.360455583	None	None	N
M/K	0.7852	likely_pathogenic	0.8817	pathogenic	-1.431	Destabilizing	0.967	D	0.625	neutral	D	0.526786933	None	None	N
M/L	0.1461	likely_benign	0.1678	benign	-0.754	Destabilizing	None	N	0.261	neutral	N	0.423483633	None	None	N
M/N	0.9446	likely_pathogenic	0.9665	pathogenic	-1.933	Destabilizing	0.999	D	0.769	deleterious	None	None	None	None	N
M/P	0.99	likely_pathogenic	0.995	pathogenic	-1.258	Destabilizing	0.985	D	0.751	deleterious	None	None	None	None	N
M/Q	0.7933	likely_pathogenic	0.8614	pathogenic	-1.524	Destabilizing	0.996	D	0.637	neutral	None	None	None	None	N
M/R	0.8043	likely_pathogenic	0.8914	pathogenic	-1.679	Destabilizing	0.985	D	0.661	neutral	N	0.495367248	None	None	N
M/S	0.9077	likely_pathogenic	0.9391	pathogenic	-2.518	Highly Destabilizing	0.956	D	0.621	neutral	None	None	None	None	N
M/T	0.7706	likely_pathogenic	0.8498	pathogenic	-2.096	Highly Destabilizing	0.907	D	0.613	neutral	N	0.506216575	None	None	N
M/V	0.179	likely_benign	0.2078	benign	-1.258	Destabilizing	0.035	N	0.365	neutral	N	0.430198961	None	None	N
M/W	0.8335	likely_pathogenic	0.8822	pathogenic	-1.126	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
M/Y	0.8264	likely_pathogenic	0.8726	pathogenic	-1.117	Destabilizing	0.992	D	0.715	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.