TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23568	70927;70928;70929	chr2:178575430;178575429;178575428	chr2:179440157;179440156;179440155
N2AB	21927	66004;66005;66006	chr2:178575430;178575429;178575428	chr2:179440157;179440156;179440155
N2A	21000	63223;63224;63225	chr2:178575430;178575429;178575428	chr2:179440157;179440156;179440155
N2B	14503	43732;43733;43734	chr2:178575430;178575429;178575428	chr2:179440157;179440156;179440155
Novex-1	14628	44107;44108;44109	chr2:178575430;178575429;178575428	chr2:179440157;179440156;179440155
Novex-2	14695	44308;44309;44310	chr2:178575430;178575429;178575428	chr2:179440157;179440156;179440155
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Fn3-59
• Domain position: 37
• Structural Position: 39
• Q(SASA): 0.1871
• 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
V/M	rs748847402	-0.901	0.967	N	0.661	0.19	0.582733548269	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
V/M	rs748847402	-0.901	0.967	N	0.661	0.19	0.582733548269	gnomAD-4.0.0	3.18351E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85932E-06	1.43303E-05	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
V/A	0.6197	likely_pathogenic	0.6684	pathogenic	-2.318	Highly Destabilizing	0.773	D	0.589	neutral	N	0.466480486	None	None	N
V/C	0.867	likely_pathogenic	0.8895	pathogenic	-1.795	Destabilizing	0.999	D	0.693	prob.neutral	None	None	None	None	N
V/D	0.8533	likely_pathogenic	0.882	pathogenic	-3.21	Highly Destabilizing	0.987	D	0.741	deleterious	None	None	None	None	N
V/E	0.7007	likely_pathogenic	0.7626	pathogenic	-3.044	Highly Destabilizing	0.983	D	0.684	prob.neutral	N	0.506970942	None	None	N
V/F	0.4459	ambiguous	0.5127	ambiguous	-1.373	Destabilizing	0.975	D	0.689	prob.neutral	None	None	None	None	N
V/G	0.7682	likely_pathogenic	0.7799	pathogenic	-2.772	Highly Destabilizing	0.983	D	0.705	prob.neutral	N	0.497208494	None	None	N
V/H	0.8581	likely_pathogenic	0.899	pathogenic	-2.448	Highly Destabilizing	0.999	D	0.755	deleterious	None	None	None	None	N
V/I	0.0798	likely_benign	0.0932	benign	-1.051	Destabilizing	0.693	D	0.604	neutral	None	None	None	None	N
V/K	0.8047	likely_pathogenic	0.858	pathogenic	-2.001	Highly Destabilizing	0.987	D	0.679	prob.neutral	None	None	None	None	N
V/L	0.3759	ambiguous	0.4543	ambiguous	-1.051	Destabilizing	0.025	N	0.401	neutral	N	0.502567987	None	None	N
V/M	0.3007	likely_benign	0.3852	ambiguous	-1.03	Destabilizing	0.967	D	0.661	neutral	N	0.472609779	None	None	N
V/N	0.732	likely_pathogenic	0.7934	pathogenic	-2.234	Highly Destabilizing	0.987	D	0.756	deleterious	None	None	None	None	N
V/P	0.9937	likely_pathogenic	0.9941	pathogenic	-1.45	Destabilizing	0.996	D	0.705	prob.neutral	None	None	None	None	N
V/Q	0.6904	likely_pathogenic	0.7689	pathogenic	-2.163	Highly Destabilizing	0.996	D	0.729	prob.delet.	None	None	None	None	N
V/R	0.7399	likely_pathogenic	0.7987	pathogenic	-1.64	Destabilizing	0.987	D	0.765	deleterious	None	None	None	None	N
V/S	0.6676	likely_pathogenic	0.7234	pathogenic	-2.733	Highly Destabilizing	0.95	D	0.649	neutral	None	None	None	None	N
V/T	0.4998	ambiguous	0.5648	pathogenic	-2.461	Highly Destabilizing	0.128	N	0.485	neutral	None	None	None	None	N
V/W	0.9586	likely_pathogenic	0.9716	pathogenic	-1.917	Destabilizing	0.999	D	0.737	prob.delet.	None	None	None	None	N
V/Y	0.8238	likely_pathogenic	0.861	pathogenic	-1.637	Destabilizing	0.987	D	0.698	prob.neutral	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.