TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5856	17791;17792;17793	chr2:178731099;178731098;178731097	chr2:179595826;179595825;179595824
N2AB	5539	16840;16841;16842	chr2:178731099;178731098;178731097	chr2:179595826;179595825;179595824
N2A	4612	14059;14060;14061	chr2:178731099;178731098;178731097	chr2:179595826;179595825;179595824
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: W
• RefSeq wild type transcript codon: TGG
• RefSeq wild type template codon: ACC
• Domain: Ig-42
• Domain position: 34
• Structural Position: 48
• Q(SASA): 0.0922
• 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
W/R	None	None	1.0	D	0.854	0.958	0.940182123992	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	None	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
W/A	0.986	likely_pathogenic	0.9886	pathogenic	-2.452	Highly Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
W/C	0.9917	likely_pathogenic	0.9948	pathogenic	-0.828	Destabilizing	1.0	D	0.765	deleterious	D	0.683331457	None	None	N
W/D	0.9992	likely_pathogenic	0.9993	pathogenic	-3.093	Highly Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
W/E	0.9988	likely_pathogenic	0.9991	pathogenic	-2.968	Highly Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
W/F	0.6853	likely_pathogenic	0.7095	pathogenic	-1.697	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
W/G	0.9666	likely_pathogenic	0.9735	pathogenic	-2.687	Highly Destabilizing	1.0	D	0.801	deleterious	D	0.683129652	None	None	N
W/H	0.9941	likely_pathogenic	0.9947	pathogenic	-2.359	Highly Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
W/I	0.9316	likely_pathogenic	0.9453	pathogenic	-1.568	Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
W/K	0.9995	likely_pathogenic	0.9996	pathogenic	-2.132	Highly Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
W/L	0.9019	likely_pathogenic	0.9212	pathogenic	-1.568	Destabilizing	1.0	D	0.801	deleterious	D	0.683129652	None	None	N
W/M	0.9753	likely_pathogenic	0.9827	pathogenic	-0.948	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
W/N	0.998	likely_pathogenic	0.9983	pathogenic	-2.874	Highly Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
W/P	0.9982	likely_pathogenic	0.9984	pathogenic	-1.889	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
W/Q	0.9992	likely_pathogenic	0.9994	pathogenic	-2.591	Highly Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
W/R	0.9988	likely_pathogenic	0.9991	pathogenic	-2.283	Highly Destabilizing	1.0	D	0.854	deleterious	D	0.683331457	None	None	N
W/S	0.9873	likely_pathogenic	0.99	pathogenic	-2.85	Highly Destabilizing	1.0	D	0.833	deleterious	D	0.683331457	None	None	N
W/T	0.9895	likely_pathogenic	0.9916	pathogenic	-2.642	Highly Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
W/V	0.9431	likely_pathogenic	0.9561	pathogenic	-1.889	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
W/Y	0.866	likely_pathogenic	0.8591	pathogenic	-1.58	Destabilizing	1.0	D	0.796	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.