TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15739	47440;47441;47442	chr2:178618243;178618242;178618241	chr2:179482970;179482969;179482968
N2AB	14098	42517;42518;42519	chr2:178618243;178618242;178618241	chr2:179482970;179482969;179482968
N2A	13171	39736;39737;39738	chr2:178618243;178618242;178618241	chr2:179482970;179482969;179482968
N2B	6674	20245;20246;20247	chr2:178618243;178618242;178618241	chr2:179482970;179482969;179482968
Novex-1	6799	20620;20621;20622	chr2:178618243;178618242;178618241	chr2:179482970;179482969;179482968
Novex-2	6866	20821;20822;20823	chr2:178618243;178618242;178618241	chr2:179482970;179482969;179482968
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Fn3-1
• Domain position: 83
• Structural Position: 115
• Q(SASA): 0.1729
• Predicted PPI site: I

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
G/D	rs2154209429	None	0.999	D	0.886	0.648	0.501308276186	gnomAD-4.0.0	1.36914E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79973E-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
G/A	0.8424	likely_pathogenic	0.904	pathogenic	-0.727	Destabilizing	0.969	D	0.657	neutral	D	0.727751021	None	None	I
G/C	0.9504	likely_pathogenic	0.9686	pathogenic	-1.069	Destabilizing	0.513	D	0.686	prob.neutral	D	0.799826702	None	None	I
G/D	0.9427	likely_pathogenic	0.96	pathogenic	-1.143	Destabilizing	0.999	D	0.886	deleterious	D	0.707471718	None	None	I
G/E	0.9711	likely_pathogenic	0.9855	pathogenic	-1.271	Destabilizing	0.999	D	0.886	deleterious	None	None	None	None	I
G/F	0.9914	likely_pathogenic	0.9951	pathogenic	-1.213	Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	I
G/H	0.9905	likely_pathogenic	0.9949	pathogenic	-1.026	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	I
G/I	0.9899	likely_pathogenic	0.9955	pathogenic	-0.66	Destabilizing	0.997	D	0.859	deleterious	None	None	None	None	I
G/K	0.9868	likely_pathogenic	0.9927	pathogenic	-1.314	Destabilizing	0.998	D	0.883	deleterious	None	None	None	None	I
G/L	0.9869	likely_pathogenic	0.9933	pathogenic	-0.66	Destabilizing	0.993	D	0.873	deleterious	None	None	None	None	I
G/M	0.9913	likely_pathogenic	0.9963	pathogenic	-0.576	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	I
G/N	0.9682	likely_pathogenic	0.9814	pathogenic	-0.985	Destabilizing	0.999	D	0.843	deleterious	None	None	None	None	I
G/P	0.9989	likely_pathogenic	0.9992	pathogenic	-0.646	Destabilizing	0.999	D	0.886	deleterious	None	None	None	None	I
G/Q	0.9759	likely_pathogenic	0.9875	pathogenic	-1.279	Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	I
G/R	0.9701	likely_pathogenic	0.9821	pathogenic	-0.807	Destabilizing	0.999	D	0.876	deleterious	D	0.729505137	None	None	I
G/S	0.7774	likely_pathogenic	0.8746	pathogenic	-1.154	Destabilizing	0.996	D	0.853	deleterious	D	0.762860697	None	None	I
G/T	0.9541	likely_pathogenic	0.9768	pathogenic	-1.219	Destabilizing	0.997	D	0.889	deleterious	None	None	None	None	I
G/V	0.9792	likely_pathogenic	0.9903	pathogenic	-0.646	Destabilizing	0.991	D	0.871	deleterious	D	0.689261531	None	None	I
G/W	0.9868	likely_pathogenic	0.9916	pathogenic	-1.399	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	I
G/Y	0.9876	likely_pathogenic	0.9929	pathogenic	-1.074	Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	I

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.