TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4975	15148;15149;15150	chr2:178735523;178735522;178735521	chr2:179600250;179600249;179600248
N2AB	4658	14197;14198;14199	chr2:178735523;178735522;178735521	chr2:179600250;179600249;179600248
N2A	3731	11416;11417;11418	chr2:178735523;178735522;178735521	chr2:179600250;179600249;179600248
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: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-32
• Domain position: 88
• Structural Position: 174
• Q(SASA): 0.1631
• 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/D	rs2081290563	None	1.0	D	0.871	0.593	0.841324563227	gnomAD-4.0.0	1.67158E-06	None	None	None	None	N	None	6.222E-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
V/A	0.4862	ambiguous	0.5724	pathogenic	-1.963	Destabilizing	0.999	D	0.634	neutral	D	0.703761902	None	None	N
V/C	0.8825	likely_pathogenic	0.9099	pathogenic	-1.949	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
V/D	0.9813	likely_pathogenic	0.988	pathogenic	-1.748	Destabilizing	1.0	D	0.871	deleterious	D	0.739674177	None	None	N
V/E	0.9444	likely_pathogenic	0.9595	pathogenic	-1.608	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
V/F	0.3361	likely_benign	0.3911	ambiguous	-1.34	Destabilizing	1.0	D	0.84	deleterious	D	0.652624752	None	None	N
V/G	0.7412	likely_pathogenic	0.8129	pathogenic	-2.433	Highly Destabilizing	1.0	D	0.869	deleterious	D	0.739674177	None	None	N
V/H	0.9759	likely_pathogenic	0.9836	pathogenic	-1.965	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
V/I	0.0782	likely_benign	0.08	benign	-0.698	Destabilizing	0.997	D	0.547	neutral	D	0.554723073	None	None	N
V/K	0.9641	likely_pathogenic	0.9734	pathogenic	-1.539	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
V/L	0.1726	likely_benign	0.2025	benign	-0.698	Destabilizing	0.997	D	0.645	neutral	N	0.320561457	None	None	N
V/M	0.1956	likely_benign	0.2198	benign	-0.882	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
V/N	0.9328	likely_pathogenic	0.9549	pathogenic	-1.65	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
V/P	0.9737	likely_pathogenic	0.9833	pathogenic	-1.088	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
V/Q	0.9432	likely_pathogenic	0.9591	pathogenic	-1.615	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
V/R	0.9477	likely_pathogenic	0.9614	pathogenic	-1.268	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
V/S	0.8173	likely_pathogenic	0.8732	pathogenic	-2.41	Highly Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
V/T	0.6498	likely_pathogenic	0.729	pathogenic	-2.118	Highly Destabilizing	0.999	D	0.661	neutral	None	None	None	None	N
V/W	0.9627	likely_pathogenic	0.9743	pathogenic	-1.601	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
V/Y	0.8788	likely_pathogenic	0.9122	pathogenic	-1.272	Destabilizing	1.0	D	0.836	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.