TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18068	54427;54428;54429	chr2:178604887;178604886;178604885	chr2:179469614;179469613;179469612
N2AB	16427	49504;49505;49506	chr2:178604887;178604886;178604885	chr2:179469614;179469613;179469612
N2A	15500	46723;46724;46725	chr2:178604887;178604886;178604885	chr2:179469614;179469613;179469612
N2B	9003	27232;27233;27234	chr2:178604887;178604886;178604885	chr2:179469614;179469613;179469612
Novex-1	9128	27607;27608;27609	chr2:178604887;178604886;178604885	chr2:179469614;179469613;179469612
Novex-2	9195	27808;27809;27810	chr2:178604887;178604886;178604885	chr2:179469614;179469613;179469612
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-19
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.2178
• 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/A	None	None	1.0	N	0.833	0.412	0.327686398923	gnomAD-4.0.0	4.79658E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.30217E-06	0	0
P/S	None	None	1.0	N	0.843	0.447	0.401042353794	gnomAD-4.0.0	6.85225E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.0031E-07	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
P/A	0.1235	likely_benign	0.1068	benign	-1.569	Destabilizing	1.0	D	0.833	deleterious	N	0.489558617	None	None	N
P/C	0.7613	likely_pathogenic	0.7461	pathogenic	-1.095	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
P/D	0.9602	likely_pathogenic	0.9405	pathogenic	-2.1	Highly Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
P/E	0.7235	likely_pathogenic	0.6755	pathogenic	-2.142	Highly Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
P/F	0.8519	likely_pathogenic	0.8482	pathogenic	-1.442	Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	N
P/G	0.7546	likely_pathogenic	0.6883	pathogenic	-1.832	Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	N
P/H	0.6789	likely_pathogenic	0.6231	pathogenic	-1.29	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
P/I	0.5922	likely_pathogenic	0.5907	pathogenic	-0.947	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
P/K	0.6417	likely_pathogenic	0.606	pathogenic	-1.261	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
P/L	0.3892	ambiguous	0.3857	ambiguous	-0.947	Destabilizing	1.0	D	0.871	deleterious	N	0.50537893	None	None	N
P/M	0.6232	likely_pathogenic	0.6275	pathogenic	-0.624	Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
P/N	0.897	likely_pathogenic	0.8595	pathogenic	-1.091	Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	N
P/Q	0.465	ambiguous	0.4211	ambiguous	-1.396	Destabilizing	1.0	D	0.843	deleterious	N	0.489614852	None	None	N
P/R	0.5067	ambiguous	0.4695	ambiguous	-0.612	Destabilizing	1.0	D	0.875	deleterious	N	0.495717691	None	None	N
P/S	0.4199	ambiguous	0.3509	ambiguous	-1.484	Destabilizing	1.0	D	0.843	deleterious	N	0.474713374	None	None	N
P/T	0.4276	ambiguous	0.3665	ambiguous	-1.437	Destabilizing	1.0	D	0.837	deleterious	N	0.500099011	None	None	N
P/V	0.4131	ambiguous	0.4081	ambiguous	-1.123	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
P/W	0.9556	likely_pathogenic	0.9517	pathogenic	-1.581	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
P/Y	0.8683	likely_pathogenic	0.8583	pathogenic	-1.314	Destabilizing	1.0	D	0.867	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.