TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19753	59482;59483;59484	chr2:178592862;178592861;178592860	chr2:179457589;179457588;179457587
N2AB	18112	54559;54560;54561	chr2:178592862;178592861;178592860	chr2:179457589;179457588;179457587
N2A	17185	51778;51779;51780	chr2:178592862;178592861;178592860	chr2:179457589;179457588;179457587
N2B	10688	32287;32288;32289	chr2:178592862;178592861;178592860	chr2:179457589;179457588;179457587
Novex-1	10813	32662;32663;32664	chr2:178592862;178592861;178592860	chr2:179457589;179457588;179457587
Novex-2	10880	32863;32864;32865	chr2:178592862;178592861;178592860	chr2:179457589;179457588;179457587
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-31
• Domain position: 74
• Structural Position: 104
• Q(SASA): 0.1012
• 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
Y/C	rs755651839	-1.391	0.265	D	0.74	0.711	0.877242521546	gnomAD-2.1.1	2.14E-05	None	None	None	None	N	None	1.23987E-04	5.66E-05	None	0	0	None	0	None	0	7.82E-06	0
Y/C	rs755651839	-1.391	0.265	D	0.74	0.711	0.877242521546	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	7.24E-05	0	0	0	0	None	0	0	1.47E-05	0	0
Y/C	rs755651839	-1.391	0.265	D	0.74	0.711	0.877242521546	gnomAD-4.0.0	8.05749E-06	None	None	None	None	N	None	5.34031E-05	3.33522E-05	None	0	2.23184E-05	None	0	0	5.08639E-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
Y/A	0.9788	likely_pathogenic	0.9728	pathogenic	-2.997	Highly Destabilizing	0.985	D	0.826	deleterious	None	None	None	None	N
Y/C	0.6504	likely_pathogenic	0.5846	pathogenic	-1.541	Destabilizing	0.265	N	0.74	deleterious	D	0.621395342	None	None	N
Y/D	0.9901	likely_pathogenic	0.988	pathogenic	-3.725	Highly Destabilizing	0.999	D	0.895	deleterious	D	0.674793212	None	None	N
Y/E	0.9951	likely_pathogenic	0.9946	pathogenic	-3.502	Highly Destabilizing	0.999	D	0.876	deleterious	None	None	None	None	N
Y/F	0.2124	likely_benign	0.1906	benign	-1.202	Destabilizing	0.135	N	0.497	neutral	D	0.576628643	None	None	N
Y/G	0.9592	likely_pathogenic	0.9548	pathogenic	-3.405	Highly Destabilizing	0.998	D	0.867	deleterious	None	None	None	None	N
Y/H	0.9087	likely_pathogenic	0.901	pathogenic	-2.415	Highly Destabilizing	0.999	D	0.763	deleterious	D	0.642522325	None	None	N
Y/I	0.9526	likely_pathogenic	0.9385	pathogenic	-1.618	Destabilizing	0.996	D	0.814	deleterious	None	None	None	None	N
Y/K	0.9963	likely_pathogenic	0.9957	pathogenic	-2.345	Highly Destabilizing	0.999	D	0.875	deleterious	None	None	None	None	N
Y/L	0.885	likely_pathogenic	0.8587	pathogenic	-1.618	Destabilizing	0.971	D	0.774	deleterious	None	None	None	None	N
Y/M	0.9615	likely_pathogenic	0.9468	pathogenic	-1.338	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
Y/N	0.9462	likely_pathogenic	0.9354	pathogenic	-3.247	Highly Destabilizing	0.999	D	0.877	deleterious	D	0.674591408	None	None	N
Y/P	0.9969	likely_pathogenic	0.9971	pathogenic	-2.096	Highly Destabilizing	0.999	D	0.891	deleterious	None	None	None	None	N
Y/Q	0.991	likely_pathogenic	0.9894	pathogenic	-2.916	Highly Destabilizing	0.999	D	0.82	deleterious	None	None	None	None	N
Y/R	0.9824	likely_pathogenic	0.9806	pathogenic	-2.308	Highly Destabilizing	0.999	D	0.877	deleterious	None	None	None	None	N
Y/S	0.9435	likely_pathogenic	0.932	pathogenic	-3.441	Highly Destabilizing	0.997	D	0.842	deleterious	D	0.674793212	None	None	N
Y/T	0.9846	likely_pathogenic	0.9802	pathogenic	-3.093	Highly Destabilizing	0.998	D	0.847	deleterious	None	None	None	None	N
Y/V	0.8817	likely_pathogenic	0.8562	pathogenic	-2.096	Highly Destabilizing	0.985	D	0.808	deleterious	None	None	None	None	N
Y/W	0.5863	likely_pathogenic	0.59	pathogenic	-0.55	Destabilizing	1.0	D	0.757	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.