TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22636	68131;68132;68133	chr2:178579124;178579123;178579122	chr2:179443851;179443850;179443849
N2AB	20995	63208;63209;63210	chr2:178579124;178579123;178579122	chr2:179443851;179443850;179443849
N2A	20068	60427;60428;60429	chr2:178579124;178579123;178579122	chr2:179443851;179443850;179443849
N2B	13571	40936;40937;40938	chr2:178579124;178579123;178579122	chr2:179443851;179443850;179443849
Novex-1	13696	41311;41312;41313	chr2:178579124;178579123;178579122	chr2:179443851;179443850;179443849
Novex-2	13763	41512;41513;41514	chr2:178579124;178579123;178579122	chr2:179443851;179443850;179443849
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-127
• Domain position: 77
• Structural Position: 172
• Q(SASA): 0.2146
• Predicted PPI site: I

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
I/L	rs1239261963	-0.187	None	N	0.141	0.132	0.242825505644	gnomAD-2.1.1	3.19E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
I/L	rs1239261963	-0.187	None	N	0.141	0.132	0.242825505644	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
I/L	rs1239261963	-0.187	None	N	0.141	0.132	0.242825505644	gnomAD-4.0.0	6.57479E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.47093E-05	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
I/A	0.8318	likely_pathogenic	0.7857	pathogenic	-1.798	Destabilizing	0.067	N	0.511	neutral	None	None	None	None	I
I/C	0.8284	likely_pathogenic	0.7918	pathogenic	-1.46	Destabilizing	0.935	D	0.602	neutral	None	None	None	None	I
I/D	0.9974	likely_pathogenic	0.9966	pathogenic	-0.643	Destabilizing	0.791	D	0.643	neutral	None	None	None	None	I
I/E	0.9937	likely_pathogenic	0.9921	pathogenic	-0.512	Destabilizing	0.555	D	0.665	neutral	None	None	None	None	I
I/F	0.2738	likely_benign	0.2309	benign	-1.003	Destabilizing	None	N	0.192	neutral	N	0.475070033	None	None	I
I/G	0.9798	likely_pathogenic	0.9713	pathogenic	-2.224	Highly Destabilizing	0.262	N	0.667	neutral	None	None	None	None	I
I/H	0.9783	likely_pathogenic	0.9723	pathogenic	-1.234	Destabilizing	0.935	D	0.639	neutral	None	None	None	None	I
I/K	0.9871	likely_pathogenic	0.9833	pathogenic	-1.125	Destabilizing	0.555	D	0.661	neutral	None	None	None	None	I
I/L	0.0941	likely_benign	0.0922	benign	-0.642	Destabilizing	None	N	0.141	neutral	N	0.494383726	None	None	I
I/M	0.2049	likely_benign	0.1746	benign	-0.79	Destabilizing	0.012	N	0.314	neutral	N	0.48617699	None	None	I
I/N	0.9707	likely_pathogenic	0.9613	pathogenic	-1.251	Destabilizing	0.741	D	0.64	neutral	N	0.516144529	None	None	I
I/P	0.9906	likely_pathogenic	0.9875	pathogenic	-1.0	Destabilizing	0.791	D	0.645	neutral	None	None	None	None	I
I/Q	0.9839	likely_pathogenic	0.9776	pathogenic	-1.169	Destabilizing	0.555	D	0.647	neutral	None	None	None	None	I
I/R	0.9736	likely_pathogenic	0.9667	pathogenic	-0.809	Destabilizing	0.555	D	0.635	neutral	None	None	None	None	I
I/S	0.9506	likely_pathogenic	0.9351	pathogenic	-2.073	Highly Destabilizing	0.211	N	0.63	neutral	D	0.526325573	None	None	I
I/T	0.9059	likely_pathogenic	0.8713	pathogenic	-1.782	Destabilizing	0.117	N	0.574	neutral	D	0.528672445	None	None	I
I/V	0.0893	likely_benign	0.0812	benign	-1.0	Destabilizing	0.012	N	0.331	neutral	N	0.473008376	None	None	I
I/W	0.9592	likely_pathogenic	0.947	pathogenic	-1.053	Destabilizing	0.935	D	0.641	neutral	None	None	None	None	I
I/Y	0.8637	likely_pathogenic	0.8374	pathogenic	-0.832	Destabilizing	0.081	N	0.627	neutral	None	None	None	None	I

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.