TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24326	73201;73202;73203	chr2:178573156;178573155;178573154	chr2:179437883;179437882;179437881
N2AB	22685	68278;68279;68280	chr2:178573156;178573155;178573154	chr2:179437883;179437882;179437881
N2A	21758	65497;65498;65499	chr2:178573156;178573155;178573154	chr2:179437883;179437882;179437881
N2B	15261	46006;46007;46008	chr2:178573156;178573155;178573154	chr2:179437883;179437882;179437881
Novex-1	15386	46381;46382;46383	chr2:178573156;178573155;178573154	chr2:179437883;179437882;179437881
Novex-2	15453	46582;46583;46584	chr2:178573156;178573155;178573154	chr2:179437883;179437882;179437881
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: Fn3-65
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.3397
• 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/L	None	None	1.0	D	0.892	0.45	0.722475063491	gnomAD-4.0.0	1.59308E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43563E-05	0
P/S	None	None	1.0	N	0.846	0.376	0.39843156188	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	None	0	0	0	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	0.1333	likely_benign	0.1689	benign	-1.322	Destabilizing	1.0	D	0.829	deleterious	N	0.505989507	None	None	N
P/C	0.6626	likely_pathogenic	0.7618	pathogenic	-0.823	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
P/D	0.9403	likely_pathogenic	0.9603	pathogenic	-1.314	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
P/E	0.7468	likely_pathogenic	0.8284	pathogenic	-1.379	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
P/F	0.7926	likely_pathogenic	0.8685	pathogenic	-1.249	Destabilizing	1.0	D	0.915	deleterious	None	None	None	None	N
P/G	0.7026	likely_pathogenic	0.792	pathogenic	-1.565	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
P/H	0.5717	likely_pathogenic	0.6943	pathogenic	-1.142	Destabilizing	1.0	D	0.894	deleterious	None	None	None	None	N
P/I	0.565	likely_pathogenic	0.6808	pathogenic	-0.778	Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	N
P/K	0.6967	likely_pathogenic	0.8164	pathogenic	-1.043	Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
P/L	0.326	likely_benign	0.4371	ambiguous	-0.778	Destabilizing	1.0	D	0.892	deleterious	D	0.54158744	None	None	N
P/M	0.5393	ambiguous	0.6461	pathogenic	-0.517	Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
P/N	0.7937	likely_pathogenic	0.8637	pathogenic	-0.718	Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
P/Q	0.4288	ambiguous	0.5577	ambiguous	-1.005	Destabilizing	1.0	D	0.863	deleterious	N	0.486323169	None	None	N
P/R	0.5597	ambiguous	0.7001	pathogenic	-0.459	Destabilizing	1.0	D	0.907	deleterious	N	0.51398653	None	None	N
P/S	0.3436	ambiguous	0.4491	ambiguous	-1.136	Destabilizing	1.0	D	0.846	deleterious	N	0.491171787	None	None	N
P/T	0.363	ambiguous	0.501	ambiguous	-1.109	Destabilizing	1.0	D	0.846	deleterious	N	0.500263595	None	None	N
P/V	0.4343	ambiguous	0.5541	ambiguous	-0.925	Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
P/W	0.938	likely_pathogenic	0.966	pathogenic	-1.353	Destabilizing	1.0	D	0.898	deleterious	None	None	None	None	N
P/Y	0.8145	likely_pathogenic	0.8894	pathogenic	-1.087	Destabilizing	1.0	D	0.919	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.