TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31094	93505;93506;93507	chr2:178548346;178548345;178548344	chr2:179413073;179413072;179413071
N2AB	29453	88582;88583;88584	chr2:178548346;178548345;178548344	chr2:179413073;179413072;179413071
N2A	28526	85801;85802;85803	chr2:178548346;178548345;178548344	chr2:179413073;179413072;179413071
N2B	22029	66310;66311;66312	chr2:178548346;178548345;178548344	chr2:179413073;179413072;179413071
Novex-1	22154	66685;66686;66687	chr2:178548346;178548345;178548344	chr2:179413073;179413072;179413071
Novex-2	22221	66886;66887;66888	chr2:178548346;178548345;178548344	chr2:179413073;179413072;179413071
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-114
• Domain position: 79
• Structural Position: 112
• Q(SASA): 0.0912
• 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
N/K	rs1698030124	None	1.0	D	0.764	0.555	0.235038932564	gnomAD-4.0.0	1.20047E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31267E-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
N/A	0.9954	likely_pathogenic	0.9951	pathogenic	-0.939	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
N/C	0.9576	likely_pathogenic	0.9571	pathogenic	-0.551	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
N/D	0.9851	likely_pathogenic	0.9816	pathogenic	-2.036	Highly Destabilizing	0.999	D	0.62	neutral	D	0.543921752	None	None	N
N/E	0.998	likely_pathogenic	0.9977	pathogenic	-1.813	Destabilizing	0.999	D	0.738	prob.delet.	None	None	None	None	N
N/F	0.9996	likely_pathogenic	0.9995	pathogenic	-0.516	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	N
N/G	0.984	likely_pathogenic	0.9833	pathogenic	-1.285	Destabilizing	0.999	D	0.575	neutral	None	None	None	None	N
N/H	0.985	likely_pathogenic	0.9829	pathogenic	-0.976	Destabilizing	1.0	D	0.778	deleterious	D	0.572194225	None	None	N
N/I	0.997	likely_pathogenic	0.9962	pathogenic	-0.024	Destabilizing	1.0	D	0.766	deleterious	D	0.572447714	None	None	N
N/K	0.9988	likely_pathogenic	0.9985	pathogenic	-0.358	Destabilizing	1.0	D	0.764	deleterious	D	0.571180266	None	None	N
N/L	0.9817	likely_pathogenic	0.9804	pathogenic	-0.024	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
N/M	0.9932	likely_pathogenic	0.9924	pathogenic	0.077	Stabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
N/P	0.998	likely_pathogenic	0.9976	pathogenic	-0.304	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
N/Q	0.9982	likely_pathogenic	0.998	pathogenic	-0.894	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
N/R	0.9977	likely_pathogenic	0.9974	pathogenic	-0.61	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
N/S	0.7675	likely_pathogenic	0.7475	pathogenic	-1.227	Destabilizing	0.999	D	0.601	neutral	D	0.528588974	None	None	N
N/T	0.9551	likely_pathogenic	0.9516	pathogenic	-0.853	Destabilizing	0.999	D	0.732	prob.delet.	N	0.510912338	None	None	N
N/V	0.9949	likely_pathogenic	0.994	pathogenic	-0.304	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
N/W	0.9998	likely_pathogenic	0.9998	pathogenic	-0.628	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
N/Y	0.9968	likely_pathogenic	0.9961	pathogenic	-0.221	Destabilizing	1.0	D	0.787	deleterious	D	0.572194225	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.