TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6404	19435;19436;19437	chr2:178728716;178728715;178728714	chr2:179593443;179593442;179593441
N2AB	6087	18484;18485;18486	chr2:178728716;178728715;178728714	chr2:179593443;179593442;179593441
N2A	5160	15703;15704;15705	chr2:178728716;178728715;178728714	chr2:179593443;179593442;179593441
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Ig-48
• Domain position: 20
• Structural Position: 30
• Q(SASA): 0.119
• 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/S	None	None	0.999	D	0.867	0.819	0.917040579573	gnomAD-4.0.0	2.05425E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.7006E-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	0.8637	likely_pathogenic	0.8649	pathogenic	-2.537	Highly Destabilizing	0.992	D	0.742	deleterious	None	None	None	None	N
L/C	0.9288	likely_pathogenic	0.9328	pathogenic	-1.984	Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	N
L/D	0.9975	likely_pathogenic	0.9978	pathogenic	-3.273	Highly Destabilizing	0.999	D	0.891	deleterious	None	None	None	None	N
L/E	0.9818	likely_pathogenic	0.9845	pathogenic	-2.954	Highly Destabilizing	0.999	D	0.891	deleterious	None	None	None	None	N
L/F	0.1807	likely_benign	0.1632	benign	-1.405	Destabilizing	0.121	N	0.335	neutral	D	0.524189345	None	None	N
L/G	0.9806	likely_pathogenic	0.9815	pathogenic	-3.167	Highly Destabilizing	0.999	D	0.885	deleterious	None	None	None	None	N
L/H	0.9415	likely_pathogenic	0.9468	pathogenic	-2.858	Highly Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
L/I	0.1561	likely_benign	0.1417	benign	-0.655	Destabilizing	0.983	D	0.605	neutral	None	None	None	None	N
L/K	0.9685	likely_pathogenic	0.9735	pathogenic	-1.887	Destabilizing	0.999	D	0.878	deleterious	None	None	None	None	N
L/M	0.1723	likely_benign	0.1639	benign	-0.912	Destabilizing	0.999	D	0.663	neutral	D	0.574773171	None	None	N
L/N	0.9891	likely_pathogenic	0.9892	pathogenic	-2.546	Highly Destabilizing	0.999	D	0.895	deleterious	None	None	None	None	N
L/P	0.9903	likely_pathogenic	0.9939	pathogenic	-1.272	Destabilizing	0.999	D	0.892	deleterious	None	None	None	None	N
L/Q	0.9221	likely_pathogenic	0.9301	pathogenic	-2.214	Highly Destabilizing	0.999	D	0.893	deleterious	None	None	None	None	N
L/R	0.9432	likely_pathogenic	0.9556	pathogenic	-1.969	Destabilizing	0.999	D	0.879	deleterious	None	None	None	None	N
L/S	0.9657	likely_pathogenic	0.9656	pathogenic	-3.171	Highly Destabilizing	0.999	D	0.867	deleterious	D	0.645633392	None	None	N
L/T	0.8995	likely_pathogenic	0.8965	pathogenic	-2.678	Highly Destabilizing	0.999	D	0.773	deleterious	None	None	None	None	N
L/V	0.2022	likely_benign	0.1964	benign	-1.272	Destabilizing	0.978	D	0.647	neutral	D	0.607245862	None	None	N
L/W	0.6019	likely_pathogenic	0.6227	pathogenic	-1.843	Destabilizing	1.0	D	0.871	deleterious	D	0.62009528	None	None	N
L/Y	0.8197	likely_pathogenic	0.8171	pathogenic	-1.582	Destabilizing	0.99	D	0.773	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.