TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15678	47257;47258;47259	chr2:178618426;178618425;178618424	chr2:179483153;179483152;179483151
N2AB	14037	42334;42335;42336	chr2:178618426;178618425;178618424	chr2:179483153;179483152;179483151
N2A	13110	39553;39554;39555	chr2:178618426;178618425;178618424	chr2:179483153;179483152;179483151
N2B	6613	20062;20063;20064	chr2:178618426;178618425;178618424	chr2:179483153;179483152;179483151
Novex-1	6738	20437;20438;20439	chr2:178618426;178618425;178618424	chr2:179483153;179483152;179483151
Novex-2	6805	20638;20639;20640	chr2:178618426;178618425;178618424	chr2:179483153;179483152;179483151
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: Fn3-1
• Domain position: 22
• Structural Position: 24
• Q(SASA): 0.122
• 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/L	None	None	0.025	D	0.688	0.685	0.82672435233	gnomAD-4.0.0	1.59404E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86257E-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
W/A	0.9976	likely_pathogenic	0.9969	pathogenic	-3.368	Highly Destabilizing	0.916	D	0.867	deleterious	None	None	None	None	N
W/C	0.9984	likely_pathogenic	0.9978	pathogenic	-1.992	Destabilizing	0.999	D	0.857	deleterious	D	0.820382476	None	None	N
W/D	0.9997	likely_pathogenic	0.9996	pathogenic	-3.509	Highly Destabilizing	0.996	D	0.901	deleterious	None	None	None	None	N
W/E	0.9997	likely_pathogenic	0.9995	pathogenic	-3.393	Highly Destabilizing	0.987	D	0.9	deleterious	None	None	None	None	N
W/F	0.7495	likely_pathogenic	0.7335	pathogenic	-2.038	Highly Destabilizing	0.975	D	0.819	deleterious	None	None	None	None	N
W/G	0.9886	likely_pathogenic	0.985	pathogenic	-3.61	Highly Destabilizing	0.983	D	0.849	deleterious	D	0.820382476	None	None	N
W/H	0.999	likely_pathogenic	0.9987	pathogenic	-2.427	Highly Destabilizing	0.999	D	0.859	deleterious	None	None	None	None	N
W/I	0.9964	likely_pathogenic	0.9949	pathogenic	-2.433	Highly Destabilizing	0.95	D	0.872	deleterious	None	None	None	None	N
W/K	0.9999	likely_pathogenic	0.9998	pathogenic	-2.628	Highly Destabilizing	0.987	D	0.9	deleterious	None	None	None	None	N
W/L	0.9894	likely_pathogenic	0.9856	pathogenic	-2.433	Highly Destabilizing	0.025	N	0.688	prob.neutral	D	0.789864669	None	None	N
W/M	0.9965	likely_pathogenic	0.9954	pathogenic	-1.936	Destabilizing	0.975	D	0.82	deleterious	None	None	None	None	N
W/N	0.9998	likely_pathogenic	0.9997	pathogenic	-3.303	Highly Destabilizing	0.996	D	0.899	deleterious	None	None	None	None	N
W/P	0.9997	likely_pathogenic	0.9996	pathogenic	-2.775	Highly Destabilizing	0.996	D	0.901	deleterious	None	None	None	None	N
W/Q	0.9998	likely_pathogenic	0.9998	pathogenic	-3.162	Highly Destabilizing	0.996	D	0.881	deleterious	None	None	None	None	N
W/R	0.9995	likely_pathogenic	0.9993	pathogenic	-2.269	Highly Destabilizing	0.983	D	0.893	deleterious	D	0.820382476	None	None	N
W/S	0.9975	likely_pathogenic	0.9966	pathogenic	-3.499	Highly Destabilizing	0.983	D	0.9	deleterious	D	0.820382476	None	None	N
W/T	0.9987	likely_pathogenic	0.998	pathogenic	-3.313	Highly Destabilizing	0.975	D	0.842	deleterious	None	None	None	None	N
W/V	0.9951	likely_pathogenic	0.9932	pathogenic	-2.775	Highly Destabilizing	0.95	D	0.862	deleterious	None	None	None	None	N
W/Y	0.973	likely_pathogenic	0.97	pathogenic	-1.877	Destabilizing	0.987	D	0.803	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.