TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22363	67312;67313;67314	chr2:178580200;178580199;178580198	chr2:179444927;179444926;179444925
N2AB	20722	62389;62390;62391	chr2:178580200;178580199;178580198	chr2:179444927;179444926;179444925
N2A	19795	59608;59609;59610	chr2:178580200;178580199;178580198	chr2:179444927;179444926;179444925
N2B	13298	40117;40118;40119	chr2:178580200;178580199;178580198	chr2:179444927;179444926;179444925
Novex-1	13423	40492;40493;40494	chr2:178580200;178580199;178580198	chr2:179444927;179444926;179444925
Novex-2	13490	40693;40694;40695	chr2:178580200;178580199;178580198	chr2:179444927;179444926;179444925
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-50
• Domain position: 10
• Structural Position: 12
• Q(SASA): 0.3108
• 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/I	rs1484693236	-0.289	0.63	N	0.58	0.131	0.483816155017	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/I	rs1484693236	-0.289	0.63	N	0.58	0.131	0.483816155017	gnomAD-4.0.0	1.59307E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43435E-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	0.4249	ambiguous	0.4097	ambiguous	-1.46	Destabilizing	0.892	D	0.512	neutral	N	0.515345283	None	None	N
V/C	0.8475	likely_pathogenic	0.8101	pathogenic	-1.121	Destabilizing	0.999	D	0.767	deleterious	None	None	None	None	N
V/D	0.9716	likely_pathogenic	0.9708	pathogenic	-1.124	Destabilizing	0.994	D	0.863	deleterious	D	0.537983496	None	None	N
V/E	0.9376	likely_pathogenic	0.9383	pathogenic	-1.054	Destabilizing	0.996	D	0.848	deleterious	None	None	None	None	N
V/F	0.5919	likely_pathogenic	0.567	pathogenic	-0.95	Destabilizing	0.056	N	0.361	neutral	N	0.476714837	None	None	N
V/G	0.709	likely_pathogenic	0.6872	pathogenic	-1.852	Destabilizing	0.983	D	0.829	deleterious	N	0.518865283	None	None	N
V/H	0.9784	likely_pathogenic	0.9757	pathogenic	-1.372	Destabilizing	0.999	D	0.833	deleterious	None	None	None	None	N
V/I	0.0957	likely_benign	0.0968	benign	-0.46	Destabilizing	0.63	D	0.58	neutral	N	0.475328244	None	None	N
V/K	0.9586	likely_pathogenic	0.9524	pathogenic	-1.245	Destabilizing	0.987	D	0.851	deleterious	None	None	None	None	N
V/L	0.4956	ambiguous	0.4599	ambiguous	-0.46	Destabilizing	0.63	D	0.511	neutral	N	0.47089194	None	None	N
V/M	0.4264	ambiguous	0.4091	ambiguous	-0.467	Destabilizing	0.987	D	0.702	prob.neutral	None	None	None	None	N
V/N	0.9219	likely_pathogenic	0.9186	pathogenic	-1.18	Destabilizing	0.996	D	0.864	deleterious	None	None	None	None	N
V/P	0.8143	likely_pathogenic	0.7922	pathogenic	-0.758	Destabilizing	0.996	D	0.858	deleterious	None	None	None	None	N
V/Q	0.9309	likely_pathogenic	0.9265	pathogenic	-1.205	Destabilizing	0.996	D	0.857	deleterious	None	None	None	None	N
V/R	0.9371	likely_pathogenic	0.9304	pathogenic	-0.887	Destabilizing	0.996	D	0.863	deleterious	None	None	None	None	N
V/S	0.7308	likely_pathogenic	0.7273	pathogenic	-1.788	Destabilizing	0.987	D	0.824	deleterious	None	None	None	None	N
V/T	0.5915	likely_pathogenic	0.5588	ambiguous	-1.579	Destabilizing	0.957	D	0.629	neutral	None	None	None	None	N
V/W	0.9818	likely_pathogenic	0.9779	pathogenic	-1.2	Destabilizing	0.999	D	0.84	deleterious	None	None	None	None	N
V/Y	0.9348	likely_pathogenic	0.9261	pathogenic	-0.868	Destabilizing	0.95	D	0.8	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.