TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32611	98056;98057;98058	chr2:178540335;178540334;178540333	chr2:179405062;179405061;179405060
N2AB	30970	93133;93134;93135	chr2:178540335;178540334;178540333	chr2:179405062;179405061;179405060
N2A	30043	90352;90353;90354	chr2:178540335;178540334;178540333	chr2:179405062;179405061;179405060
N2B	23546	70861;70862;70863	chr2:178540335;178540334;178540333	chr2:179405062;179405061;179405060
Novex-1	23671	71236;71237;71238	chr2:178540335;178540334;178540333	chr2:179405062;179405061;179405060
Novex-2	23738	71437;71438;71439	chr2:178540335;178540334;178540333	chr2:179405062;179405061;179405060
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: Fn3-126
• Domain position: 12
• Structural Position: 14
• Q(SASA): 0.4938
• 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/H	None	None	1.0	N	0.687	0.457	0.378674557249	gnomAD-4.0.0	3.18398E-06	None	None	None	None	N	None	0	0	None	0	5.546E-05	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
D/A	0.7658	likely_pathogenic	0.7302	pathogenic	-0.191	Destabilizing	1.0	D	0.757	deleterious	N	0.474811825	None	None	N
D/C	0.9713	likely_pathogenic	0.9648	pathogenic	0.364	Stabilizing	1.0	D	0.696	prob.neutral	None	None	None	None	N
D/E	0.6271	likely_pathogenic	0.5586	ambiguous	-0.294	Destabilizing	1.0	D	0.381	neutral	N	0.518382801	None	None	N
D/F	0.9765	likely_pathogenic	0.9722	pathogenic	-0.458	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
D/G	0.7843	likely_pathogenic	0.7542	pathogenic	-0.377	Destabilizing	1.0	D	0.768	deleterious	N	0.485207079	None	None	N
D/H	0.9144	likely_pathogenic	0.9008	pathogenic	-0.626	Destabilizing	1.0	D	0.687	prob.neutral	N	0.498755884	None	None	N
D/I	0.9659	likely_pathogenic	0.9586	pathogenic	0.244	Stabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
D/K	0.9561	likely_pathogenic	0.9428	pathogenic	0.46	Stabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
D/L	0.9473	likely_pathogenic	0.9377	pathogenic	0.244	Stabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
D/M	0.9795	likely_pathogenic	0.9749	pathogenic	0.604	Stabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
D/N	0.4192	ambiguous	0.3847	ambiguous	0.286	Stabilizing	1.0	D	0.653	neutral	N	0.469202738	None	None	N
D/P	0.9986	likely_pathogenic	0.9984	pathogenic	0.121	Stabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
D/Q	0.9279	likely_pathogenic	0.9038	pathogenic	0.293	Stabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	N
D/R	0.9569	likely_pathogenic	0.9426	pathogenic	0.356	Stabilizing	1.0	D	0.756	deleterious	None	None	None	None	N
D/S	0.632	likely_pathogenic	0.574	pathogenic	0.178	Stabilizing	1.0	D	0.69	prob.neutral	None	None	None	None	N
D/T	0.8917	likely_pathogenic	0.8707	pathogenic	0.321	Stabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
D/V	0.8946	likely_pathogenic	0.8774	pathogenic	0.121	Stabilizing	1.0	D	0.797	deleterious	N	0.497488437	None	None	N
D/W	0.9959	likely_pathogenic	0.995	pathogenic	-0.437	Destabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	N
D/Y	0.8619	likely_pathogenic	0.8376	pathogenic	-0.242	Destabilizing	1.0	D	0.718	prob.delet.	D	0.526735188	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.