TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26107	78544;78545;78546	chr2:178567813;178567812;178567811	chr2:179432540;179432539;179432538
N2AB	24466	73621;73622;73623	chr2:178567813;178567812;178567811	chr2:179432540;179432539;179432538
N2A	23539	70840;70841;70842	chr2:178567813;178567812;178567811	chr2:179432540;179432539;179432538
N2B	17042	51349;51350;51351	chr2:178567813;178567812;178567811	chr2:179432540;179432539;179432538
Novex-1	17167	51724;51725;51726	chr2:178567813;178567812;178567811	chr2:179432540;179432539;179432538
Novex-2	17234	51925;51926;51927	chr2:178567813;178567812;178567811	chr2:179432540;179432539;179432538
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTA
• RefSeq wild type template codon: AAT
• Domain: Fn3-78
• Domain position: 20
• Structural Position: 22
• Q(SASA): 0.1317
• 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	rs2154166544	None	1.0	D	0.892	0.612	0.854974579623	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	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
L/A	0.9702	likely_pathogenic	0.9578	pathogenic	-2.862	Highly Destabilizing	0.999	D	0.699	prob.neutral	None	None	None	None	N
L/C	0.9386	likely_pathogenic	0.9217	pathogenic	-1.773	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
L/D	0.9998	likely_pathogenic	0.9997	pathogenic	-3.38	Highly Destabilizing	1.0	D	0.922	deleterious	None	None	None	None	N
L/E	0.9984	likely_pathogenic	0.9973	pathogenic	-3.065	Highly Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
L/F	0.8257	likely_pathogenic	0.7467	pathogenic	-1.616	Destabilizing	1.0	D	0.753	deleterious	N	0.516962271	None	None	N
L/G	0.996	likely_pathogenic	0.9949	pathogenic	-3.429	Highly Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
L/H	0.9968	likely_pathogenic	0.9943	pathogenic	-3.086	Highly Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
L/I	0.1228	likely_benign	0.0942	benign	-1.128	Destabilizing	0.999	D	0.553	neutral	N	0.501586552	None	None	N
L/K	0.9976	likely_pathogenic	0.9963	pathogenic	-2.073	Highly Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
L/M	0.3958	ambiguous	0.3027	benign	-1.339	Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	N
L/N	0.9983	likely_pathogenic	0.9973	pathogenic	-2.793	Highly Destabilizing	1.0	D	0.925	deleterious	None	None	None	None	N
L/P	0.9983	likely_pathogenic	0.9974	pathogenic	-1.702	Destabilizing	1.0	D	0.927	deleterious	None	None	None	None	N
L/Q	0.9944	likely_pathogenic	0.9907	pathogenic	-2.417	Highly Destabilizing	1.0	D	0.92	deleterious	None	None	None	None	N
L/R	0.9949	likely_pathogenic	0.9921	pathogenic	-2.183	Highly Destabilizing	1.0	D	0.908	deleterious	None	None	None	None	N
L/S	0.9956	likely_pathogenic	0.993	pathogenic	-3.239	Highly Destabilizing	1.0	D	0.892	deleterious	D	0.55608407	None	None	N
L/T	0.9736	likely_pathogenic	0.9624	pathogenic	-2.773	Highly Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
L/V	0.1673	likely_benign	0.134	benign	-1.702	Destabilizing	0.999	D	0.571	neutral	N	0.519649451	None	None	N
L/W	0.9921	likely_pathogenic	0.9851	pathogenic	-1.93	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
L/Y	0.9908	likely_pathogenic	0.9848	pathogenic	-1.846	Destabilizing	1.0	D	0.831	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.