TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31607	95044;95045;95046	chr2:178546609;178546608;178546607	chr2:179411336;179411335;179411334
N2AB	29966	90121;90122;90123	chr2:178546609;178546608;178546607	chr2:179411336;179411335;179411334
N2A	29039	87340;87341;87342	chr2:178546609;178546608;178546607	chr2:179411336;179411335;179411334
N2B	22542	67849;67850;67851	chr2:178546609;178546608;178546607	chr2:179411336;179411335;179411334
Novex-1	22667	68224;68225;68226	chr2:178546609;178546608;178546607	chr2:179411336;179411335;179411334
Novex-2	22734	68425;68426;68427	chr2:178546609;178546608;178546607	chr2:179411336;179411335;179411334
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-118
• Domain position: 102
• Structural Position: 132
• Q(SASA): 1.2097
• 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
D/N	None	None	1.0	N	0.762	0.279	0.396645960531	gnomAD-4.0.0	3.20977E-06	None	None	None	None	N	None	0	2.29274E-05	None	0	0	None	0	0	2.89337E-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
D/A	0.7329	likely_pathogenic	0.7486	pathogenic	-0.173	Destabilizing	1.0	D	0.72	deleterious	N	0.506816226	None	None	N
D/C	0.9842	likely_pathogenic	0.9868	pathogenic	0.094	Stabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
D/E	0.6972	likely_pathogenic	0.738	pathogenic	-0.264	Destabilizing	0.999	D	0.531	neutral	N	0.465142962	None	None	N
D/F	0.9797	likely_pathogenic	0.9829	pathogenic	-0.237	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
D/G	0.8028	likely_pathogenic	0.822	pathogenic	-0.35	Destabilizing	1.0	D	0.774	deleterious	N	0.477806657	None	None	N
D/H	0.9347	likely_pathogenic	0.947	pathogenic	-0.097	Destabilizing	1.0	D	0.871	deleterious	N	0.484554607	None	None	N
D/I	0.9681	likely_pathogenic	0.9717	pathogenic	0.239	Stabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
D/K	0.9628	likely_pathogenic	0.9706	pathogenic	0.297	Stabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
D/L	0.9312	likely_pathogenic	0.9363	pathogenic	0.239	Stabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
D/M	0.9762	likely_pathogenic	0.9808	pathogenic	0.342	Stabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
D/N	0.5553	ambiguous	0.5981	pathogenic	0.14	Stabilizing	1.0	D	0.762	deleterious	N	0.468020514	None	None	N
D/P	0.9701	likely_pathogenic	0.9709	pathogenic	0.123	Stabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
D/Q	0.9382	likely_pathogenic	0.9521	pathogenic	0.152	Stabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
D/R	0.9655	likely_pathogenic	0.9721	pathogenic	0.425	Stabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
D/S	0.6582	likely_pathogenic	0.7072	pathogenic	0.013	Stabilizing	1.0	D	0.776	deleterious	None	None	None	None	N
D/T	0.8896	likely_pathogenic	0.9055	pathogenic	0.143	Stabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
D/V	0.8958	likely_pathogenic	0.9072	pathogenic	0.123	Stabilizing	1.0	D	0.769	deleterious	N	0.494643464	None	None	N
D/W	0.9938	likely_pathogenic	0.9949	pathogenic	-0.165	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	N
D/Y	0.8592	likely_pathogenic	0.878	pathogenic	-0.017	Destabilizing	1.0	D	0.824	deleterious	N	0.507267217	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.