TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21159	63700;63701;63702	chr2:178587932;178587931;178587930	chr2:179452659;179452658;179452657
N2AB	19518	58777;58778;58779	chr2:178587932;178587931;178587930	chr2:179452659;179452658;179452657
N2A	18591	55996;55997;55998	chr2:178587932;178587931;178587930	chr2:179452659;179452658;179452657
N2B	12094	36505;36506;36507	chr2:178587932;178587931;178587930	chr2:179452659;179452658;179452657
Novex-1	12219	36880;36881;36882	chr2:178587932;178587931;178587930	chr2:179452659;179452658;179452657
Novex-2	12286	37081;37082;37083	chr2:178587932;178587931;178587930	chr2:179452659;179452658;179452657
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Fn3-41
• Domain position: 96
• Structural Position: 123
• Q(SASA): 0.1582
• 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
L/P	None	None	0.999	N	0.89	0.454	0.544346501278	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
L/V	rs1218951803	-1.187	0.429	N	0.347	0.113	0.230578612272	gnomAD-2.1.1	4.23E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.44E-06	0
L/V	rs1218951803	-1.187	0.429	N	0.347	0.113	0.230578612272	gnomAD-4.0.0	1.61256E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.89907E-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
L/A	0.4704	ambiguous	0.4493	ambiguous	-2.149	Highly Destabilizing	0.987	D	0.642	neutral	None	None	None	None	N
L/C	0.5984	likely_pathogenic	0.5939	pathogenic	-1.351	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
L/D	0.9115	likely_pathogenic	0.9029	pathogenic	-2.138	Highly Destabilizing	0.999	D	0.907	deleterious	None	None	None	None	N
L/E	0.6751	likely_pathogenic	0.6448	pathogenic	-1.958	Destabilizing	0.999	D	0.869	deleterious	None	None	None	None	N
L/F	0.2931	likely_benign	0.2885	benign	-1.198	Destabilizing	0.998	D	0.861	deleterious	None	None	None	None	N
L/G	0.6818	likely_pathogenic	0.6476	pathogenic	-2.646	Highly Destabilizing	0.999	D	0.855	deleterious	None	None	None	None	N
L/H	0.5803	likely_pathogenic	0.5517	ambiguous	-1.974	Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
L/I	0.1288	likely_benign	0.1301	benign	-0.749	Destabilizing	0.966	D	0.633	neutral	N	0.463998451	None	None	N
L/K	0.5641	likely_pathogenic	0.5202	ambiguous	-1.703	Destabilizing	0.999	D	0.807	deleterious	None	None	None	None	N
L/M	0.1333	likely_benign	0.1362	benign	-0.639	Destabilizing	0.998	D	0.805	deleterious	None	None	None	None	N
L/N	0.67	likely_pathogenic	0.648	pathogenic	-1.885	Destabilizing	0.999	D	0.915	deleterious	None	None	None	None	N
L/P	0.7285	likely_pathogenic	0.7048	pathogenic	-1.193	Destabilizing	0.999	D	0.89	deleterious	N	0.432462036	None	None	N
L/Q	0.3475	ambiguous	0.322	benign	-1.811	Destabilizing	0.999	D	0.903	deleterious	N	0.458601722	None	None	N
L/R	0.5052	ambiguous	0.4672	ambiguous	-1.365	Destabilizing	0.999	D	0.874	deleterious	N	0.465096182	None	None	N
L/S	0.629	likely_pathogenic	0.6039	pathogenic	-2.56	Highly Destabilizing	0.998	D	0.827	deleterious	None	None	None	None	N
L/T	0.4315	ambiguous	0.4244	ambiguous	-2.238	Highly Destabilizing	0.996	D	0.783	deleterious	None	None	None	None	N
L/V	0.1506	likely_benign	0.152	benign	-1.193	Destabilizing	0.429	N	0.347	neutral	N	0.418860807	None	None	N
L/W	0.4582	ambiguous	0.4431	ambiguous	-1.513	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
L/Y	0.5809	likely_pathogenic	0.5741	pathogenic	-1.208	Destabilizing	0.999	D	0.821	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.