TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34403	103432;103433;103434	chr2:178533408;178533407;178533406	chr2:179398135;179398134;179398133
N2AB	32762	98509;98510;98511	chr2:178533408;178533407;178533406	chr2:179398135;179398134;179398133
N2A	31835	95728;95729;95730	chr2:178533408;178533407;178533406	chr2:179398135;179398134;179398133
N2B	25338	76237;76238;76239	chr2:178533408;178533407;178533406	chr2:179398135;179398134;179398133
Novex-1	25463	76612;76613;76614	chr2:178533408;178533407;178533406	chr2:179398135;179398134;179398133
Novex-2	25530	76813;76814;76815	chr2:178533408;178533407;178533406	chr2:179398135;179398134;179398133
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-162
• Domain position: 41
• Structural Position: 58
• Q(SASA): 0.1881
• 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
L/V	rs773892755	-1.148	0.999	N	0.51	0.405	0.541466613703	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
L/V	rs773892755	-1.148	0.999	N	0.51	0.405	0.541466613703	gnomAD-4.0.0	6.8422E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15934E-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
L/A	0.9423	likely_pathogenic	0.9384	pathogenic	-2.239	Highly Destabilizing	0.999	D	0.696	prob.neutral	None	None	None	None	N
L/C	0.9605	likely_pathogenic	0.9592	pathogenic	-1.449	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
L/D	0.9991	likely_pathogenic	0.999	pathogenic	-1.998	Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
L/E	0.9938	likely_pathogenic	0.9934	pathogenic	-1.828	Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
L/F	0.7725	likely_pathogenic	0.7212	pathogenic	-1.371	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
L/G	0.9951	likely_pathogenic	0.9947	pathogenic	-2.709	Highly Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
L/H	0.9875	likely_pathogenic	0.9854	pathogenic	-1.885	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
L/I	0.1626	likely_benign	0.1427	benign	-0.917	Destabilizing	0.999	D	0.527	neutral	None	None	None	None	N
L/K	0.9887	likely_pathogenic	0.9883	pathogenic	-1.666	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
L/M	0.4807	ambiguous	0.4554	ambiguous	-0.806	Destabilizing	1.0	D	0.737	prob.delet.	N	0.49394626	None	None	N
L/N	0.9951	likely_pathogenic	0.9947	pathogenic	-1.82	Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
L/P	0.9754	likely_pathogenic	0.9774	pathogenic	-1.335	Destabilizing	1.0	D	0.863	deleterious	D	0.530181223	None	None	N
L/Q	0.9804	likely_pathogenic	0.9787	pathogenic	-1.759	Destabilizing	1.0	D	0.845	deleterious	D	0.523686763	None	None	N
L/R	0.9771	likely_pathogenic	0.9762	pathogenic	-1.315	Destabilizing	1.0	D	0.85	deleterious	D	0.541537528	None	None	N
L/S	0.9919	likely_pathogenic	0.9907	pathogenic	-2.514	Highly Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
L/T	0.9582	likely_pathogenic	0.9562	pathogenic	-2.195	Highly Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
L/V	0.2219	likely_benign	0.2059	benign	-1.335	Destabilizing	0.999	D	0.51	neutral	N	0.461567592	None	None	N
L/W	0.9765	likely_pathogenic	0.9708	pathogenic	-1.572	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
L/Y	0.9785	likely_pathogenic	0.9738	pathogenic	-1.313	Destabilizing	1.0	D	0.832	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.