TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17700	53323;53324;53325	chr2:178607590;178607589;178607588	chr2:179472317;179472316;179472315
N2AB	16059	48400;48401;48402	chr2:178607590;178607589;178607588	chr2:179472317;179472316;179472315
N2A	15132	45619;45620;45621	chr2:178607590;178607589;178607588	chr2:179472317;179472316;179472315
N2B	8635	26128;26129;26130	chr2:178607590;178607589;178607588	chr2:179472317;179472316;179472315
Novex-1	8760	26503;26504;26505	chr2:178607590;178607589;178607588	chr2:179472317;179472316;179472315
Novex-2	8827	26704;26705;26706	chr2:178607590;178607589;178607588	chr2:179472317;179472316;179472315
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Ig-113
• Domain position: 24
• Structural Position: 42
• Q(SASA): 0.5869
• 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
P/L	rs767647740	0.055	1.0	D	0.739	0.624	0.719680077433	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
P/L	rs767647740	0.055	1.0	D	0.739	0.624	0.719680077433	gnomAD-4.0.0	1.59242E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43299E-05	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
P/A	0.9502	likely_pathogenic	0.9625	pathogenic	-0.476	Destabilizing	1.0	D	0.725	prob.delet.	D	0.576926799	None	None	I
P/C	0.995	likely_pathogenic	0.9968	pathogenic	-0.511	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	I
P/D	0.987	likely_pathogenic	0.9877	pathogenic	-0.429	Destabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	I
P/E	0.9832	likely_pathogenic	0.9868	pathogenic	-0.556	Destabilizing	1.0	D	0.728	prob.delet.	None	None	None	None	I
P/F	0.9972	likely_pathogenic	0.9982	pathogenic	-0.783	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	I
P/G	0.9777	likely_pathogenic	0.9839	pathogenic	-0.595	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	I
P/H	0.9816	likely_pathogenic	0.9867	pathogenic	-0.229	Destabilizing	1.0	D	0.753	deleterious	D	0.64265633	None	None	I
P/I	0.9832	likely_pathogenic	0.9859	pathogenic	-0.314	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	I
P/K	0.9841	likely_pathogenic	0.9878	pathogenic	-0.445	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	I
P/L	0.9518	likely_pathogenic	0.9612	pathogenic	-0.314	Destabilizing	1.0	D	0.739	prob.delet.	D	0.617118218	None	None	I
P/M	0.987	likely_pathogenic	0.9906	pathogenic	-0.307	Destabilizing	1.0	D	0.756	deleterious	None	None	None	None	I
P/N	0.986	likely_pathogenic	0.9888	pathogenic	-0.106	Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	I
P/Q	0.9776	likely_pathogenic	0.9849	pathogenic	-0.385	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	I
P/R	0.9673	likely_pathogenic	0.9756	pathogenic	0.099	Stabilizing	1.0	D	0.753	deleterious	D	0.61671461	None	None	I
P/S	0.9824	likely_pathogenic	0.9863	pathogenic	-0.424	Destabilizing	1.0	D	0.731	prob.delet.	D	0.57641982	None	None	I
P/T	0.9547	likely_pathogenic	0.9642	pathogenic	-0.457	Destabilizing	1.0	D	0.726	prob.delet.	D	0.642252722	None	None	I
P/V	0.9687	likely_pathogenic	0.9733	pathogenic	-0.333	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	I
P/W	0.9981	likely_pathogenic	0.9987	pathogenic	-0.86	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	I
P/Y	0.9951	likely_pathogenic	0.9968	pathogenic	-0.562	Destabilizing	1.0	D	0.777	deleterious	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.