TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28287	85084;85085;85086	chr2:178561273;178561272;178561271	chr2:179426000;179425999;179425998
N2AB	26646	80161;80162;80163	chr2:178561273;178561272;178561271	chr2:179426000;179425999;179425998
N2A	25719	77380;77381;77382	chr2:178561273;178561272;178561271	chr2:179426000;179425999;179425998
N2B	19222	57889;57890;57891	chr2:178561273;178561272;178561271	chr2:179426000;179425999;179425998
Novex-1	19347	58264;58265;58266	chr2:178561273;178561272;178561271	chr2:179426000;179425999;179425998
Novex-2	19414	58465;58466;58467	chr2:178561273;178561272;178561271	chr2:179426000;179425999;179425998
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Fn3-94
• Domain position: 36
• Structural Position: 38
• Q(SASA): 0.1045
• 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
Y/F	rs1559296734	None	0.434	D	0.399	0.646	0.572173585829	gnomAD-4.0.0	3.42107E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.49724E-06	0	0
Y/H	rs1406227768	None	1.0	D	0.752	0.841	0.733173517768	gnomAD-4.0.0	1.59128E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85806E-06	0	0
Y/N	None	None	1.0	D	0.869	0.822	0.903800418731	gnomAD-4.0.0	1.59128E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85806E-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
Y/A	0.998	likely_pathogenic	0.9985	pathogenic	-3.706	Highly Destabilizing	0.998	D	0.786	deleterious	None	None	None	None	N
Y/C	0.9401	likely_pathogenic	0.9554	pathogenic	-2.017	Highly Destabilizing	1.0	D	0.848	deleterious	D	0.667424714	None	None	N
Y/D	0.9975	likely_pathogenic	0.9978	pathogenic	-3.944	Highly Destabilizing	1.0	D	0.896	deleterious	D	0.667828322	None	None	N
Y/E	0.9994	likely_pathogenic	0.9995	pathogenic	-3.728	Highly Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
Y/F	0.2834	likely_benign	0.3075	benign	-1.564	Destabilizing	0.434	N	0.399	neutral	D	0.550152999	None	None	N
Y/G	0.9933	likely_pathogenic	0.9944	pathogenic	-4.103	Highly Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	N
Y/H	0.9856	likely_pathogenic	0.9893	pathogenic	-2.811	Highly Destabilizing	1.0	D	0.752	deleterious	D	0.641886602	None	None	N
Y/I	0.9831	likely_pathogenic	0.985	pathogenic	-2.349	Highly Destabilizing	0.999	D	0.774	deleterious	None	None	None	None	N
Y/K	0.9993	likely_pathogenic	0.9994	pathogenic	-2.63	Highly Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
Y/L	0.9609	likely_pathogenic	0.9659	pathogenic	-2.349	Highly Destabilizing	0.994	D	0.715	prob.delet.	None	None	None	None	N
Y/M	0.9877	likely_pathogenic	0.9902	pathogenic	-2.034	Highly Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
Y/N	0.9814	likely_pathogenic	0.985	pathogenic	-3.411	Highly Destabilizing	1.0	D	0.869	deleterious	D	0.667828322	None	None	N
Y/P	0.9995	likely_pathogenic	0.9996	pathogenic	-2.823	Highly Destabilizing	1.0	D	0.902	deleterious	None	None	None	None	N
Y/Q	0.999	likely_pathogenic	0.9992	pathogenic	-3.145	Highly Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
Y/R	0.9972	likely_pathogenic	0.9975	pathogenic	-2.381	Highly Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
Y/S	0.9916	likely_pathogenic	0.9935	pathogenic	-3.7	Highly Destabilizing	1.0	D	0.861	deleterious	D	0.667828322	None	None	N
Y/T	0.9975	likely_pathogenic	0.9981	pathogenic	-3.368	Highly Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
Y/V	0.9737	likely_pathogenic	0.9768	pathogenic	-2.823	Highly Destabilizing	0.997	D	0.732	prob.delet.	None	None	None	None	N
Y/W	0.8688	likely_pathogenic	0.8847	pathogenic	-0.772	Destabilizing	1.0	D	0.734	prob.delet.	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.