TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25175	75748;75749;75750	chr2:178570609;178570608;178570607	chr2:179435336;179435335;179435334
N2AB	23534	70825;70826;70827	chr2:178570609;178570608;178570607	chr2:179435336;179435335;179435334
N2A	22607	68044;68045;68046	chr2:178570609;178570608;178570607	chr2:179435336;179435335;179435334
N2B	16110	48553;48554;48555	chr2:178570609;178570608;178570607	chr2:179435336;179435335;179435334
Novex-1	16235	48928;48929;48930	chr2:178570609;178570608;178570607	chr2:179435336;179435335;179435334
Novex-2	16302	49129;49130;49131	chr2:178570609;178570608;178570607	chr2:179435336;179435335;179435334
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Ig-134
• Domain position: 65
• Structural Position: 145
• Q(SASA): 0.3237
• 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	rs1231900798	None	None	N	0.135	0.074	0.243972157842	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
V/A	rs1231900798	None	None	N	0.135	0.074	0.243972157842	gnomAD-4.0.0	6.5767E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47102E-05	0	0
V/I	rs537603113	-0.282	None	N	0.125	0.113	0.124217242631	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	6.54E-05	None	0	0	0
V/I	rs537603113	-0.282	None	N	0.125	0.113	0.124217242631	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.07211E-04	0
V/I	rs537603113	-0.282	None	N	0.125	0.113	0.124217242631	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	0	None	None	0	0	None	None	None	1E-03	None
V/I	rs537603113	-0.282	None	N	0.125	0.113	0.124217242631	gnomAD-4.0.0	8.0573E-06	None	None	None	None	N	None	1.33344E-05	0	None	0	0	None	0	0	0	1.31767E-04	0
V/L	rs537603113	-0.395	0.002	N	0.212	0.071	0.107399877778	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
V/L	rs537603113	-0.395	0.002	N	0.212	0.071	0.107399877778	gnomAD-4.0.0	2.053E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69869E-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	0.1643	likely_benign	0.16	benign	-0.91	Destabilizing	None	N	0.135	neutral	N	0.475701965	None	None	N
V/C	0.5426	ambiguous	0.5948	pathogenic	-0.766	Destabilizing	0.356	N	0.455	neutral	None	None	None	None	N
V/D	0.3608	ambiguous	0.3654	ambiguous	-0.591	Destabilizing	0.072	N	0.5	neutral	None	None	None	None	N
V/E	0.3184	likely_benign	0.3146	benign	-0.684	Destabilizing	0.055	N	0.515	neutral	N	0.444877625	None	None	N
V/F	0.153	likely_benign	0.1585	benign	-1.02	Destabilizing	None	N	0.167	neutral	None	None	None	None	N
V/G	0.2001	likely_benign	0.2013	benign	-1.097	Destabilizing	None	N	0.184	neutral	D	0.532595397	None	None	N
V/H	0.4909	ambiguous	0.5024	ambiguous	-0.63	Destabilizing	0.628	D	0.474	neutral	None	None	None	None	N
V/I	0.0649	likely_benign	0.0693	benign	-0.549	Destabilizing	None	N	0.125	neutral	N	0.441533463	None	None	N
V/K	0.3126	likely_benign	0.3002	benign	-0.673	Destabilizing	0.072	N	0.519	neutral	None	None	None	None	N
V/L	0.1166	likely_benign	0.1269	benign	-0.549	Destabilizing	0.002	N	0.212	neutral	N	0.499002899	None	None	N
V/M	0.1113	likely_benign	0.1145	benign	-0.372	Destabilizing	0.214	N	0.359	neutral	None	None	None	None	N
V/N	0.2025	likely_benign	0.2058	benign	-0.424	Destabilizing	0.214	N	0.527	neutral	None	None	None	None	N
V/P	0.7423	likely_pathogenic	0.7737	pathogenic	-0.633	Destabilizing	0.356	N	0.533	neutral	None	None	None	None	N
V/Q	0.279	likely_benign	0.2728	benign	-0.702	Destabilizing	0.356	N	0.493	neutral	None	None	None	None	N
V/R	0.2728	likely_benign	0.2712	benign	-0.113	Destabilizing	0.214	N	0.525	neutral	None	None	None	None	N
V/S	0.1543	likely_benign	0.1532	benign	-0.87	Destabilizing	0.016	N	0.424	neutral	None	None	None	None	N
V/T	0.1505	likely_benign	0.1447	benign	-0.863	Destabilizing	0.001	N	0.135	neutral	None	None	None	None	N
V/W	0.7409	likely_pathogenic	0.7734	pathogenic	-1.085	Destabilizing	0.864	D	0.473	neutral	None	None	None	None	N
V/Y	0.4683	ambiguous	0.4892	ambiguous	-0.786	Destabilizing	0.038	N	0.53	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.