TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30910	92953;92954;92955	chr2:178548898;178548897;178548896	chr2:179413625;179413624;179413623
N2AB	29269	88030;88031;88032	chr2:178548898;178548897;178548896	chr2:179413625;179413624;179413623
N2A	28342	85249;85250;85251	chr2:178548898;178548897;178548896	chr2:179413625;179413624;179413623
N2B	21845	65758;65759;65760	chr2:178548898;178548897;178548896	chr2:179413625;179413624;179413623
Novex-1	21970	66133;66134;66135	chr2:178548898;178548897;178548896	chr2:179413625;179413624;179413623
Novex-2	22037	66334;66335;66336	chr2:178548898;178548897;178548896	chr2:179413625;179413624;179413623
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: Fn3-113
• Domain position: 90
• Structural Position: 123
• Q(SASA): 0.1733
• 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	rs1698264334	None	0.002	N	0.489	0.13	0.181679512989	gnomAD-4.0.0	1.59119E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43271E-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	0.1992	likely_benign	0.1699	benign	-1.562	Destabilizing	None	N	0.276	neutral	N	0.47771711	None	None	N
V/C	0.7541	likely_pathogenic	0.7321	pathogenic	-1.164	Destabilizing	0.685	D	0.639	neutral	None	None	None	None	N
V/D	0.6064	likely_pathogenic	0.5723	pathogenic	-1.577	Destabilizing	0.221	N	0.702	prob.delet.	None	None	None	None	N
V/E	0.5712	likely_pathogenic	0.5238	ambiguous	-1.469	Destabilizing	0.058	N	0.663	prob.neutral	N	0.488934181	None	None	N
V/F	0.2534	likely_benign	0.233	benign	-0.947	Destabilizing	0.221	N	0.759	deleterious	None	None	None	None	N
V/G	0.2911	likely_benign	0.2746	benign	-1.999	Destabilizing	0.03	N	0.627	neutral	N	0.48932973	None	None	N
V/H	0.8246	likely_pathogenic	0.7953	pathogenic	-1.684	Destabilizing	0.869	D	0.679	prob.neutral	None	None	None	None	N
V/I	0.0822	likely_benign	0.0813	benign	-0.415	Destabilizing	0.016	N	0.597	neutral	None	None	None	None	N
V/K	0.7335	likely_pathogenic	0.7032	pathogenic	-1.342	Destabilizing	0.075	N	0.657	prob.neutral	None	None	None	None	N
V/L	0.2145	likely_benign	0.1948	benign	-0.415	Destabilizing	0.005	N	0.529	neutral	N	0.4469142	None	None	N
V/M	0.1666	likely_benign	0.1552	benign	-0.446	Destabilizing	0.002	N	0.489	neutral	N	0.502903556	None	None	N
V/N	0.4854	ambiguous	0.4359	ambiguous	-1.348	Destabilizing	0.366	N	0.705	prob.delet.	None	None	None	None	N
V/P	0.7159	likely_pathogenic	0.7053	pathogenic	-0.764	Destabilizing	0.221	N	0.689	prob.delet.	None	None	None	None	N
V/Q	0.6537	likely_pathogenic	0.6032	pathogenic	-1.341	Destabilizing	0.366	N	0.689	prob.delet.	None	None	None	None	N
V/R	0.7298	likely_pathogenic	0.6912	pathogenic	-1.056	Destabilizing	0.221	N	0.705	prob.delet.	None	None	None	None	N
V/S	0.3324	likely_benign	0.2892	benign	-1.945	Destabilizing	0.039	N	0.607	neutral	None	None	None	None	N
V/T	0.2456	likely_benign	0.2092	benign	-1.705	Destabilizing	0.001	N	0.335	neutral	None	None	None	None	N
V/W	0.8953	likely_pathogenic	0.8848	pathogenic	-1.309	Destabilizing	0.869	D	0.717	prob.delet.	None	None	None	None	N
V/Y	0.6839	likely_pathogenic	0.6485	pathogenic	-0.934	Destabilizing	0.366	N	0.736	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.