TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24327	73204;73205;73206	chr2:178573153;178573152;178573151	chr2:179437880;179437879;179437878
N2AB	22686	68281;68282;68283	chr2:178573153;178573152;178573151	chr2:179437880;179437879;179437878
N2A	21759	65500;65501;65502	chr2:178573153;178573152;178573151	chr2:179437880;179437879;179437878
N2B	15262	46009;46010;46011	chr2:178573153;178573152;178573151	chr2:179437880;179437879;179437878
Novex-1	15387	46384;46385;46386	chr2:178573153;178573152;178573151	chr2:179437880;179437879;179437878
Novex-2	15454	46585;46586;46587	chr2:178573153;178573152;178573151	chr2:179437880;179437879;179437878
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: 5
• Structural Position: 5
• Q(SASA): 0.1251
• 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/Q	rs748006828	-1.857	0.988	D	0.855	0.54	0.686611096917	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
P/Q	rs748006828	-1.857	0.988	D	0.855	0.54	0.686611096917	gnomAD-4.0.0	1.59301E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86092E-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
P/A	0.7402	likely_pathogenic	0.7189	pathogenic	-2.24	Highly Destabilizing	0.919	D	0.784	deleterious	D	0.525875582	None	None	N
P/C	0.9734	likely_pathogenic	0.9722	pathogenic	-1.862	Destabilizing	1.0	D	0.928	deleterious	None	None	None	None	N
P/D	0.9997	likely_pathogenic	0.9996	pathogenic	-3.146	Highly Destabilizing	0.991	D	0.835	deleterious	None	None	None	None	N
P/E	0.9988	likely_pathogenic	0.9985	pathogenic	-2.951	Highly Destabilizing	0.991	D	0.824	deleterious	None	None	None	None	N
P/F	0.9995	likely_pathogenic	0.9992	pathogenic	-1.288	Destabilizing	0.999	D	0.947	deleterious	None	None	None	None	N
P/G	0.9935	likely_pathogenic	0.9924	pathogenic	-2.754	Highly Destabilizing	0.938	D	0.865	deleterious	None	None	None	None	N
P/H	0.9986	likely_pathogenic	0.9982	pathogenic	-2.556	Highly Destabilizing	1.0	D	0.917	deleterious	None	None	None	None	N
P/I	0.9618	likely_pathogenic	0.9461	pathogenic	-0.803	Destabilizing	0.995	D	0.925	deleterious	None	None	None	None	N
P/K	0.9992	likely_pathogenic	0.9991	pathogenic	-2.054	Highly Destabilizing	0.991	D	0.833	deleterious	None	None	None	None	N
P/L	0.927	likely_pathogenic	0.9163	pathogenic	-0.803	Destabilizing	0.988	D	0.924	deleterious	D	0.572679929	None	None	N
P/M	0.9906	likely_pathogenic	0.9872	pathogenic	-0.869	Destabilizing	1.0	D	0.921	deleterious	None	None	None	None	N
P/N	0.9994	likely_pathogenic	0.9992	pathogenic	-2.306	Highly Destabilizing	0.991	D	0.905	deleterious	None	None	None	None	N
P/Q	0.9975	likely_pathogenic	0.9969	pathogenic	-2.189	Highly Destabilizing	0.988	D	0.855	deleterious	D	0.54795631	None	None	N
P/R	0.9966	likely_pathogenic	0.996	pathogenic	-1.791	Destabilizing	0.988	D	0.906	deleterious	D	0.573947377	None	None	N
P/S	0.982	likely_pathogenic	0.9775	pathogenic	-2.848	Highly Destabilizing	0.414	N	0.688	prob.neutral	D	0.551323671	None	None	N
P/T	0.9588	likely_pathogenic	0.9261	pathogenic	-2.526	Highly Destabilizing	0.976	D	0.803	deleterious	D	0.573440398	None	None	N
P/V	0.8707	likely_pathogenic	0.823	pathogenic	-1.256	Destabilizing	0.991	D	0.91	deleterious	None	None	None	None	N
P/W	0.9999	likely_pathogenic	0.9998	pathogenic	-1.865	Destabilizing	1.0	D	0.898	deleterious	None	None	None	None	N
P/Y	0.9997	likely_pathogenic	0.9996	pathogenic	-1.529	Destabilizing	1.0	D	0.948	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.