TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15084	45475;45476;45477	chr2:178621574;178621573;178621572	chr2:179486301;179486300;179486299
N2AB	13443	40552;40553;40554	chr2:178621574;178621573;178621572	chr2:179486301;179486300;179486299
N2A	12516	37771;37772;37773	chr2:178621574;178621573;178621572	chr2:179486301;179486300;179486299
N2B	6019	18280;18281;18282	chr2:178621574;178621573;178621572	chr2:179486301;179486300;179486299
Novex-1	6144	18655;18656;18657	chr2:178621574;178621573;178621572	chr2:179486301;179486300;179486299
Novex-2	6211	18856;18857;18858	chr2:178621574;178621573;178621572	chr2:179486301;179486300;179486299
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-102
• Domain position: 54
• Structural Position: 135
• Q(SASA): 0.2454
• 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/E	None	None	0.989	D	0.477	0.421	0.464270400615	gnomAD-4.0.0	3.18747E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.72554E-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	0.6707	likely_pathogenic	0.7388	pathogenic	-0.638	Destabilizing	0.996	D	0.584	neutral	None	None	None	None	N
K/C	0.8511	likely_pathogenic	0.8895	pathogenic	-0.798	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
K/D	0.8038	likely_pathogenic	0.8403	pathogenic	-0.521	Destabilizing	0.999	D	0.795	deleterious	None	None	None	None	N
K/E	0.3115	likely_benign	0.3313	benign	-0.389	Destabilizing	0.989	D	0.477	neutral	D	0.563623679	None	None	N
K/F	0.9106	likely_pathogenic	0.9216	pathogenic	-0.213	Destabilizing	1.0	D	0.756	deleterious	None	None	None	None	N
K/G	0.7154	likely_pathogenic	0.764	pathogenic	-1.036	Destabilizing	0.999	D	0.715	prob.delet.	None	None	None	None	N
K/H	0.4619	ambiguous	0.5187	ambiguous	-1.381	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
K/I	0.5816	likely_pathogenic	0.5981	pathogenic	0.405	Stabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
K/L	0.5657	likely_pathogenic	0.6125	pathogenic	0.405	Stabilizing	0.999	D	0.715	prob.delet.	None	None	None	None	N
K/M	0.4028	ambiguous	0.4278	ambiguous	0.254	Stabilizing	1.0	D	0.756	deleterious	N	0.514892436	None	None	N
K/N	0.5777	likely_pathogenic	0.6192	pathogenic	-0.817	Destabilizing	0.998	D	0.668	neutral	D	0.558526952	None	None	N
K/P	0.9634	likely_pathogenic	0.9691	pathogenic	0.087	Stabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
K/Q	0.1776	likely_benign	0.1902	benign	-0.852	Destabilizing	0.997	D	0.668	neutral	N	0.502838344	None	None	N
K/R	0.1012	likely_benign	0.1064	benign	-0.861	Destabilizing	0.217	N	0.196	neutral	N	0.472774991	None	None	N
K/S	0.6357	likely_pathogenic	0.6939	pathogenic	-1.428	Destabilizing	0.996	D	0.551	neutral	None	None	None	None	N
K/T	0.3357	likely_benign	0.3872	ambiguous	-1.083	Destabilizing	0.998	D	0.741	deleterious	N	0.508692277	None	None	N
K/V	0.5622	ambiguous	0.6011	pathogenic	0.087	Stabilizing	0.999	D	0.764	deleterious	None	None	None	None	N
K/W	0.8691	likely_pathogenic	0.8886	pathogenic	-0.114	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
K/Y	0.7807	likely_pathogenic	0.8149	pathogenic	0.186	Stabilizing	1.0	D	0.777	deleterious	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.