TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21995	66208;66209;66210	chr2:178582473;178582472;178582471	chr2:179447200;179447199;179447198
N2AB	20354	61285;61286;61287	chr2:178582473;178582472;178582471	chr2:179447200;179447199;179447198
N2A	19427	58504;58505;58506	chr2:178582473;178582472;178582471	chr2:179447200;179447199;179447198
N2B	12930	39013;39014;39015	chr2:178582473;178582472;178582471	chr2:179447200;179447199;179447198
Novex-1	13055	39388;39389;39390	chr2:178582473;178582472;178582471	chr2:179447200;179447199;179447198
Novex-2	13122	39589;39590;39591	chr2:178582473;178582472;178582471	chr2:179447200;179447199;179447198
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-47
• Domain position: 40
• Structural Position: 42
• Q(SASA): 0.2517
• 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
K/R	rs773998370	-0.696	0.032	N	0.467	0.153	0.241664281697	gnomAD-2.1.1	8.07E-06	None	None	None	None	N	None	0	2.91E-05	None	0	0	None	0	None	0	8.92E-06	0
K/R	rs773998370	-0.696	0.032	N	0.467	0.153	0.241664281697	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
K/R	rs773998370	-0.696	0.032	N	0.467	0.153	0.241664281697	gnomAD-4.0.0	3.84756E-06	None	None	None	None	N	None	0	1.69618E-05	None	0	0	None	0	0	4.79099E-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
K/A	0.9951	likely_pathogenic	0.996	pathogenic	-1.51	Destabilizing	0.754	D	0.665	neutral	None	None	None	None	N
K/C	0.9816	likely_pathogenic	0.9829	pathogenic	-1.389	Destabilizing	0.998	D	0.771	deleterious	None	None	None	None	N
K/D	0.9995	likely_pathogenic	0.9997	pathogenic	-2.21	Highly Destabilizing	0.978	D	0.688	prob.neutral	None	None	None	None	N
K/E	0.9946	likely_pathogenic	0.9953	pathogenic	-1.87	Destabilizing	0.822	D	0.663	neutral	N	0.517630154	None	None	N
K/F	0.9962	likely_pathogenic	0.998	pathogenic	-0.726	Destabilizing	0.956	D	0.788	deleterious	None	None	None	None	N
K/G	0.9969	likely_pathogenic	0.9973	pathogenic	-2.002	Highly Destabilizing	0.978	D	0.713	prob.delet.	None	None	None	None	N
K/H	0.946	likely_pathogenic	0.9583	pathogenic	-1.719	Destabilizing	0.998	D	0.715	prob.delet.	None	None	None	None	N
K/I	0.9832	likely_pathogenic	0.9858	pathogenic	-0.086	Destabilizing	0.89	D	0.77	deleterious	N	0.478406223	None	None	N
K/L	0.9728	likely_pathogenic	0.9785	pathogenic	-0.086	Destabilizing	0.514	D	0.7	prob.neutral	None	None	None	None	N
K/M	0.9519	likely_pathogenic	0.9609	pathogenic	-0.523	Destabilizing	0.304	N	0.612	neutral	None	None	None	None	N
K/N	0.9987	likely_pathogenic	0.999	pathogenic	-1.863	Destabilizing	0.971	D	0.631	neutral	D	0.528986459	None	None	N
K/P	0.9997	likely_pathogenic	0.9998	pathogenic	-0.545	Destabilizing	0.993	D	0.706	prob.neutral	None	None	None	None	N
K/Q	0.9323	likely_pathogenic	0.9363	pathogenic	-1.407	Destabilizing	0.942	D	0.648	neutral	N	0.470065338	None	None	N
K/R	0.1808	likely_benign	0.1925	benign	-0.818	Destabilizing	0.032	N	0.467	neutral	N	0.466089899	None	None	N
K/S	0.9976	likely_pathogenic	0.9979	pathogenic	-2.325	Highly Destabilizing	0.86	D	0.649	neutral	None	None	None	None	N
K/T	0.9878	likely_pathogenic	0.9891	pathogenic	-1.721	Destabilizing	0.942	D	0.675	neutral	N	0.493485511	None	None	N
K/V	0.9742	likely_pathogenic	0.9774	pathogenic	-0.545	Destabilizing	0.754	D	0.705	prob.neutral	None	None	None	None	N
K/W	0.9937	likely_pathogenic	0.9959	pathogenic	-0.814	Destabilizing	0.998	D	0.751	deleterious	None	None	None	None	N
K/Y	0.9835	likely_pathogenic	0.989	pathogenic	-0.467	Destabilizing	0.978	D	0.76	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.