TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6177	18754;18755;18756	chr2:178729724;178729723;178729722	chr2:179594451;179594450;179594449
N2AB	5860	17803;17804;17805	chr2:178729724;178729723;178729722	chr2:179594451;179594450;179594449
N2A	4933	15022;15023;15024	chr2:178729724;178729723;178729722	chr2:179594451;179594450;179594449
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-45
• Domain position: 73
• Structural Position: 155
• Q(SASA): 0.1815
• 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/A	rs2080061909	None	0.954	N	0.602	0.19	0.668390147402	gnomAD-4.0.0	1.59135E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85856E-06	0	0
V/L	None	None	0.91	N	0.58	0.206	0.611224490431	gnomAD-4.0.0	6.00161E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.25001E-06	0	3.66327E-05
V/M	rs1553921514	None	0.998	N	0.612	0.286	0.63694057803	gnomAD-4.0.0	4.80129E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.25001E-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
V/A	0.2215	likely_benign	0.1975	benign	-1.714	Destabilizing	0.954	D	0.602	neutral	N	0.508545102	None	None	N
V/C	0.7574	likely_pathogenic	0.7623	pathogenic	-1.459	Destabilizing	1.0	D	0.696	prob.neutral	None	None	None	None	N
V/D	0.4187	ambiguous	0.3786	ambiguous	-2.012	Highly Destabilizing	0.999	D	0.749	deleterious	None	None	None	None	N
V/E	0.3007	likely_benign	0.263	benign	-1.841	Destabilizing	0.998	D	0.654	neutral	N	0.472776303	None	None	N
V/F	0.1279	likely_benign	0.1197	benign	-1.023	Destabilizing	0.942	D	0.601	neutral	None	None	None	None	N
V/G	0.3055	likely_benign	0.2738	benign	-2.196	Highly Destabilizing	0.998	D	0.686	prob.neutral	N	0.495074079	None	None	N
V/H	0.4693	ambiguous	0.4307	ambiguous	-1.928	Destabilizing	0.991	D	0.795	deleterious	None	None	None	None	N
V/I	0.0729	likely_benign	0.0736	benign	-0.399	Destabilizing	0.965	D	0.612	neutral	None	None	None	None	N
V/K	0.3459	ambiguous	0.2998	benign	-1.159	Destabilizing	0.996	D	0.652	neutral	None	None	None	None	N
V/L	0.2	likely_benign	0.1807	benign	-0.399	Destabilizing	0.91	D	0.58	neutral	N	0.509065177	None	None	N
V/M	0.14	likely_benign	0.1314	benign	-0.609	Destabilizing	0.998	D	0.612	neutral	N	0.477608906	None	None	N
V/N	0.293	likely_benign	0.2703	benign	-1.354	Destabilizing	0.999	D	0.783	deleterious	None	None	None	None	N
V/P	0.9682	likely_pathogenic	0.9686	pathogenic	-0.808	Destabilizing	0.999	D	0.711	prob.delet.	None	None	None	None	N
V/Q	0.2979	likely_benign	0.2621	benign	-1.269	Destabilizing	0.999	D	0.733	prob.delet.	None	None	None	None	N
V/R	0.2577	likely_benign	0.2252	benign	-1.049	Destabilizing	0.996	D	0.785	deleterious	None	None	None	None	N
V/S	0.2023	likely_benign	0.1851	benign	-2.004	Highly Destabilizing	0.996	D	0.653	neutral	None	None	None	None	N
V/T	0.1522	likely_benign	0.1448	benign	-1.695	Destabilizing	0.985	D	0.571	neutral	None	None	None	None	N
V/W	0.7271	likely_pathogenic	0.7063	pathogenic	-1.446	Destabilizing	0.999	D	0.787	deleterious	None	None	None	None	N
V/Y	0.4252	ambiguous	0.4075	ambiguous	-1.062	Destabilizing	0.155	N	0.43	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.