TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28574	85945;85946;85947	chr2:178560412;178560411;178560410	chr2:179425139;179425138;179425137
N2AB	26933	81022;81023;81024	chr2:178560412;178560411;178560410	chr2:179425139;179425138;179425137
N2A	26006	78241;78242;78243	chr2:178560412;178560411;178560410	chr2:179425139;179425138;179425137
N2B	19509	58750;58751;58752	chr2:178560412;178560411;178560410	chr2:179425139;179425138;179425137
Novex-1	19634	59125;59126;59127	chr2:178560412;178560411;178560410	chr2:179425139;179425138;179425137
Novex-2	19701	59326;59327;59328	chr2:178560412;178560411;178560410	chr2:179425139;179425138;179425137
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Fn3-96
• Domain position: 25
• Structural Position: 27
• Q(SASA): 0.1664
• 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
P/S	None	None	0.568	N	0.553	0.466	0.304108284078	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	3.66327E-05

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	0.8094	likely_pathogenic	0.7837	pathogenic	-2.05	Highly Destabilizing	0.955	D	0.7	prob.neutral	N	0.501182783	None	None	N
P/C	0.9806	likely_pathogenic	0.9753	pathogenic	-1.771	Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
P/D	0.9967	likely_pathogenic	0.9957	pathogenic	-2.698	Highly Destabilizing	0.995	D	0.827	deleterious	None	None	None	None	N
P/E	0.9914	likely_pathogenic	0.9882	pathogenic	-2.596	Highly Destabilizing	0.995	D	0.82	deleterious	None	None	None	None	N
P/F	0.9984	likely_pathogenic	0.9976	pathogenic	-1.488	Destabilizing	0.999	D	0.899	deleterious	None	None	None	None	N
P/G	0.9736	likely_pathogenic	0.9663	pathogenic	-2.488	Highly Destabilizing	0.966	D	0.805	deleterious	None	None	None	None	N
P/H	0.9893	likely_pathogenic	0.9845	pathogenic	-2.156	Highly Destabilizing	1.0	D	0.881	deleterious	D	0.538405251	None	None	N
P/I	0.9871	likely_pathogenic	0.9825	pathogenic	-0.879	Destabilizing	0.998	D	0.893	deleterious	None	None	None	None	N
P/K	0.9946	likely_pathogenic	0.992	pathogenic	-1.769	Destabilizing	0.995	D	0.826	deleterious	None	None	None	None	N
P/L	0.9253	likely_pathogenic	0.901	pathogenic	-0.879	Destabilizing	0.993	D	0.882	deleterious	D	0.548151714	None	None	N
P/M	0.9856	likely_pathogenic	0.9815	pathogenic	-0.807	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
P/N	0.9947	likely_pathogenic	0.9931	pathogenic	-1.858	Destabilizing	0.995	D	0.895	deleterious	None	None	None	None	N
P/Q	0.9851	likely_pathogenic	0.9777	pathogenic	-1.909	Destabilizing	0.998	D	0.843	deleterious	None	None	None	None	N
P/R	0.9858	likely_pathogenic	0.9794	pathogenic	-1.353	Destabilizing	0.993	D	0.885	deleterious	D	0.526795456	None	None	N
P/S	0.9466	likely_pathogenic	0.9354	pathogenic	-2.41	Highly Destabilizing	0.568	D	0.553	neutral	N	0.507183491	None	None	N
P/T	0.9212	likely_pathogenic	0.9038	pathogenic	-2.184	Highly Destabilizing	0.987	D	0.797	deleterious	D	0.540607297	None	None	N
P/V	0.9609	likely_pathogenic	0.951	pathogenic	-1.239	Destabilizing	0.995	D	0.88	deleterious	None	None	None	None	N
P/W	0.9989	likely_pathogenic	0.9984	pathogenic	-1.879	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
P/Y	0.9983	likely_pathogenic	0.9973	pathogenic	-1.557	Destabilizing	1.0	D	0.897	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.