TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14061	42406;42407;42408	chr2:178634600;178634599;178634598	chr2:179499327;179499326;179499325
N2AB	12420	37483;37484;37485	chr2:178634600;178634599;178634598	chr2:179499327;179499326;179499325
N2A	11493	34702;34703;34704	chr2:178634600;178634599;178634598	chr2:179499327;179499326;179499325
N2B	4996	15211;15212;15213	chr2:178634600;178634599;178634598	chr2:179499327;179499326;179499325
Novex-1	5121	15586;15587;15588	chr2:178634600;178634599;178634598	chr2:179499327;179499326;179499325
Novex-2	5188	15787;15788;15789	chr2:178634600;178634599;178634598	chr2:179499327;179499326;179499325
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-91
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.6064
• 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
K/M	None	None	0.976	D	0.655	0.569	0.557365556891	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
K/A	0.4876	ambiguous	0.5381	ambiguous	-0.04	Destabilizing	0.399	N	0.561	neutral	None	None	None	None	N
K/C	0.8611	likely_pathogenic	0.86	pathogenic	-0.347	Destabilizing	0.982	D	0.687	prob.neutral	None	None	None	None	N
K/D	0.7425	likely_pathogenic	0.7714	pathogenic	-0.003	Destabilizing	0.7	D	0.681	prob.neutral	None	None	None	None	N
K/E	0.2012	likely_benign	0.2448	benign	0.05	Stabilizing	0.201	N	0.527	neutral	N	0.493507113	None	None	N
K/F	0.9218	likely_pathogenic	0.9362	pathogenic	-0.017	Destabilizing	0.947	D	0.665	neutral	None	None	None	None	N
K/G	0.6358	likely_pathogenic	0.6404	pathogenic	-0.298	Destabilizing	0.7	D	0.539	neutral	None	None	None	None	N
K/H	0.4569	ambiguous	0.482	ambiguous	-0.492	Destabilizing	0.947	D	0.664	neutral	None	None	None	None	N
K/I	0.5732	likely_pathogenic	0.6543	pathogenic	0.579	Stabilizing	0.826	D	0.695	prob.neutral	None	None	None	None	N
K/L	0.5493	ambiguous	0.5973	pathogenic	0.579	Stabilizing	0.7	D	0.539	neutral	None	None	None	None	N
K/M	0.3916	ambiguous	0.4574	ambiguous	0.112	Stabilizing	0.976	D	0.655	neutral	D	0.59703418	None	None	N
K/N	0.5543	ambiguous	0.6071	pathogenic	-0.03	Destabilizing	0.638	D	0.654	neutral	D	0.543654392	None	None	N
K/P	0.8786	likely_pathogenic	0.8984	pathogenic	0.402	Stabilizing	0.826	D	0.699	prob.neutral	None	None	None	None	N
K/Q	0.1561	likely_benign	0.1796	benign	-0.095	Destabilizing	0.638	D	0.658	neutral	N	0.497327958	None	None	N
K/R	0.1029	likely_benign	0.1077	benign	-0.195	Destabilizing	0.002	N	0.225	neutral	N	0.497226076	None	None	N
K/S	0.5616	ambiguous	0.6083	pathogenic	-0.483	Destabilizing	0.399	N	0.593	neutral	None	None	None	None	N
K/T	0.2419	likely_benign	0.3179	benign	-0.262	Destabilizing	0.638	D	0.63	neutral	N	0.518077105	None	None	N
K/V	0.5172	ambiguous	0.5956	pathogenic	0.402	Stabilizing	0.7	D	0.649	neutral	None	None	None	None	N
K/W	0.9153	likely_pathogenic	0.9238	pathogenic	-0.047	Destabilizing	0.982	D	0.697	prob.neutral	None	None	None	None	N
K/Y	0.85	likely_pathogenic	0.8678	pathogenic	0.28	Stabilizing	0.826	D	0.658	neutral	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.