TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21226	63901;63902;63903	chr2:178587633;178587632;178587631	chr2:179452360;179452359;179452358
N2AB	19585	58978;58979;58980	chr2:178587633;178587632;178587631	chr2:179452360;179452359;179452358
N2A	18658	56197;56198;56199	chr2:178587633;178587632;178587631	chr2:179452360;179452359;179452358
N2B	12161	36706;36707;36708	chr2:178587633;178587632;178587631	chr2:179452360;179452359;179452358
Novex-1	12286	37081;37082;37083	chr2:178587633;178587632;178587631	chr2:179452360;179452359;179452358
Novex-2	12353	37282;37283;37284	chr2:178587633;178587632;178587631	chr2:179452360;179452359;179452358
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-123
• Domain position: 50
• Structural Position: 131
• Q(SASA): 0.9051
• Predicted PPI site: I

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/G	rs879061715	None	1.0	N	0.595	0.468	None	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.625E-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	0.7092	likely_pathogenic	0.6654	pathogenic	0.006	Stabilizing	1.0	D	0.603	neutral	N	0.458845666	None	None	I
D/C	0.9502	likely_pathogenic	0.9401	pathogenic	-0.161	Destabilizing	1.0	D	0.678	prob.neutral	None	None	None	None	I
D/E	0.5088	ambiguous	0.4474	ambiguous	-0.324	Destabilizing	1.0	D	0.41	neutral	N	0.469137699	None	None	I
D/F	0.9752	likely_pathogenic	0.9683	pathogenic	-0.072	Destabilizing	1.0	D	0.665	neutral	None	None	None	None	I
D/G	0.493	ambiguous	0.4242	ambiguous	-0.11	Destabilizing	1.0	D	0.595	neutral	N	0.463246302	None	None	I
D/H	0.8331	likely_pathogenic	0.7897	pathogenic	0.521	Stabilizing	1.0	D	0.607	neutral	N	0.478697894	None	None	I
D/I	0.9645	likely_pathogenic	0.9573	pathogenic	0.244	Stabilizing	1.0	D	0.671	neutral	None	None	None	None	I
D/K	0.9075	likely_pathogenic	0.8817	pathogenic	0.399	Stabilizing	1.0	D	0.615	neutral	None	None	None	None	I
D/L	0.9277	likely_pathogenic	0.9157	pathogenic	0.244	Stabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	I
D/M	0.9738	likely_pathogenic	0.9691	pathogenic	0.039	Stabilizing	1.0	D	0.673	neutral	None	None	None	None	I
D/N	0.3987	ambiguous	0.3454	ambiguous	0.148	Stabilizing	1.0	D	0.569	neutral	N	0.491571841	None	None	I
D/P	0.9192	likely_pathogenic	0.9045	pathogenic	0.184	Stabilizing	1.0	D	0.619	neutral	None	None	None	None	I
D/Q	0.8492	likely_pathogenic	0.8177	pathogenic	0.151	Stabilizing	1.0	D	0.611	neutral	None	None	None	None	I
D/R	0.899	likely_pathogenic	0.8798	pathogenic	0.64	Stabilizing	1.0	D	0.653	neutral	None	None	None	None	I
D/S	0.501	ambiguous	0.4487	ambiguous	0.058	Stabilizing	1.0	D	0.583	neutral	None	None	None	None	I
D/T	0.8411	likely_pathogenic	0.808	pathogenic	0.154	Stabilizing	1.0	D	0.616	neutral	None	None	None	None	I
D/V	0.8868	likely_pathogenic	0.8721	pathogenic	0.184	Stabilizing	1.0	D	0.685	prob.neutral	N	0.482990309	None	None	I
D/W	0.9882	likely_pathogenic	0.9866	pathogenic	-0.029	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	I
D/Y	0.811	likely_pathogenic	0.778	pathogenic	0.151	Stabilizing	1.0	D	0.656	neutral	N	0.476242359	None	None	I

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.