TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26913	80962;80963;80964	chr2:178565395;178565394;178565393	chr2:179430122;179430121;179430120
N2AB	25272	76039;76040;76041	chr2:178565395;178565394;178565393	chr2:179430122;179430121;179430120
N2A	24345	73258;73259;73260	chr2:178565395;178565394;178565393	chr2:179430122;179430121;179430120
N2B	17848	53767;53768;53769	chr2:178565395;178565394;178565393	chr2:179430122;179430121;179430120
Novex-1	17973	54142;54143;54144	chr2:178565395;178565394;178565393	chr2:179430122;179430121;179430120
Novex-2	18040	54343;54344;54345	chr2:178565395;178565394;178565393	chr2:179430122;179430121;179430120
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-139
• Domain position: 34
• Structural Position: 48
• Q(SASA): 0.2654
• 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/S	rs1705368893	None	0.967	D	0.841	0.834	0.95226174331	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
W/S	rs1705368893	None	0.967	D	0.841	0.834	0.95226174331	gnomAD-4.0.0	6.57601E-06	None	None	None	None	N	None	2.41406E-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	0.9901	likely_pathogenic	0.988	pathogenic	-2.77	Highly Destabilizing	0.845	D	0.824	deleterious	None	None	None	None	N
W/C	0.9947	likely_pathogenic	0.9934	pathogenic	-2.068	Highly Destabilizing	0.056	N	0.732	prob.delet.	D	0.721174295	None	None	N
W/D	0.9997	likely_pathogenic	0.9996	pathogenic	-2.911	Highly Destabilizing	0.996	D	0.828	deleterious	None	None	None	None	N
W/E	0.9993	likely_pathogenic	0.9991	pathogenic	-2.774	Highly Destabilizing	0.996	D	0.834	deleterious	None	None	None	None	N
W/F	0.4477	ambiguous	0.444	ambiguous	-1.647	Destabilizing	0.987	D	0.795	deleterious	None	None	None	None	N
W/G	0.9827	likely_pathogenic	0.9776	pathogenic	-3.037	Highly Destabilizing	0.983	D	0.817	deleterious	D	0.720972491	None	None	N
W/H	0.9958	likely_pathogenic	0.9947	pathogenic	-2.147	Highly Destabilizing	0.999	D	0.817	deleterious	None	None	None	None	N
W/I	0.9303	likely_pathogenic	0.9125	pathogenic	-1.775	Destabilizing	0.975	D	0.84	deleterious	None	None	None	None	N
W/K	0.9996	likely_pathogenic	0.9994	pathogenic	-2.581	Highly Destabilizing	0.987	D	0.834	deleterious	None	None	None	None	N
W/L	0.8381	likely_pathogenic	0.8235	pathogenic	-1.775	Destabilizing	0.805	D	0.805	deleterious	D	0.695434379	None	None	N
W/M	0.9683	likely_pathogenic	0.9592	pathogenic	-1.54	Destabilizing	0.999	D	0.789	deleterious	None	None	None	None	N
W/N	0.9994	likely_pathogenic	0.9993	pathogenic	-3.31	Highly Destabilizing	0.996	D	0.842	deleterious	None	None	None	None	N
W/P	0.9987	likely_pathogenic	0.9987	pathogenic	-2.135	Highly Destabilizing	0.996	D	0.843	deleterious	None	None	None	None	N
W/Q	0.9993	likely_pathogenic	0.9992	pathogenic	-3.032	Highly Destabilizing	0.996	D	0.835	deleterious	None	None	None	None	N
W/R	0.9986	likely_pathogenic	0.9982	pathogenic	-2.502	Highly Destabilizing	0.994	D	0.84	deleterious	D	0.721174295	None	None	N
W/S	0.9931	likely_pathogenic	0.9912	pathogenic	-3.526	Highly Destabilizing	0.967	D	0.841	deleterious	D	0.721174295	None	None	N
W/T	0.9926	likely_pathogenic	0.9904	pathogenic	-3.315	Highly Destabilizing	0.975	D	0.811	deleterious	None	None	None	None	N
W/V	0.9362	likely_pathogenic	0.9236	pathogenic	-2.135	Highly Destabilizing	0.975	D	0.836	deleterious	None	None	None	None	N
W/Y	0.9045	likely_pathogenic	0.8922	pathogenic	-1.517	Destabilizing	0.996	D	0.801	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.