TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25447	76564;76565;76566	chr2:178569793;178569792;178569791	chr2:179434520;179434519;179434518
N2AB	23806	71641;71642;71643	chr2:178569793;178569792;178569791	chr2:179434520;179434519;179434518
N2A	22879	68860;68861;68862	chr2:178569793;178569792;178569791	chr2:179434520;179434519;179434518
N2B	16382	49369;49370;49371	chr2:178569793;178569792;178569791	chr2:179434520;179434519;179434518
Novex-1	16507	49744;49745;49746	chr2:178569793;178569792;178569791	chr2:179434520;179434519;179434518
Novex-2	16574	49945;49946;49947	chr2:178569793;178569792;178569791	chr2:179434520;179434519;179434518
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: Fn3-73
• Domain position: 43
• Structural Position: 50
• Q(SASA): 0.4666
• 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/L	rs374106281	-0.506	None	N	0.141	0.106	0.278143212241	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
V/L	rs374106281	-0.506	None	N	0.141	0.106	0.278143212241	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/L	rs374106281	-0.506	None	N	0.141	0.106	0.278143212241	gnomAD-4.0.0	1.30178E-05	None	None	None	None	N	None	0	1.66789E-05	None	0	0	None	0	0	1.6955E-05	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	0.0842	likely_benign	0.0871	benign	-1.29	Destabilizing	None	N	0.15	neutral	N	0.423973917	None	None	N
V/C	0.5019	ambiguous	0.5393	ambiguous	-0.762	Destabilizing	0.356	N	0.397	neutral	None	None	None	None	N
V/D	0.1986	likely_benign	0.1859	benign	-1.0	Destabilizing	0.072	N	0.502	neutral	None	None	None	None	N
V/E	0.1984	likely_benign	0.1867	benign	-1.066	Destabilizing	0.055	N	0.449	neutral	N	0.499047679	None	None	N
V/F	0.1416	likely_benign	0.1398	benign	-1.272	Destabilizing	0.214	N	0.423	neutral	None	None	None	None	N
V/G	0.1136	likely_benign	0.1075	benign	-1.532	Destabilizing	None	N	0.267	neutral	N	0.456606411	None	None	N
V/H	0.3597	ambiguous	0.3702	ambiguous	-1.032	Destabilizing	0.864	D	0.475	neutral	None	None	None	None	N
V/I	0.0708	likely_benign	0.0728	benign	-0.754	Destabilizing	0.016	N	0.274	neutral	None	None	None	None	N
V/K	0.1655	likely_benign	0.167	benign	-0.882	Destabilizing	0.072	N	0.449	neutral	None	None	None	None	N
V/L	0.1202	likely_benign	0.1315	benign	-0.754	Destabilizing	None	N	0.141	neutral	N	0.467148691	None	None	N
V/M	0.1006	likely_benign	0.1043	benign	-0.438	Destabilizing	0.171	N	0.331	neutral	N	0.484423838	None	None	N
V/N	0.1271	likely_benign	0.1376	benign	-0.566	Destabilizing	0.072	N	0.48	neutral	None	None	None	None	N
V/P	0.2306	likely_benign	0.2557	benign	-0.897	Destabilizing	0.356	N	0.493	neutral	None	None	None	None	N
V/Q	0.2136	likely_benign	0.2169	benign	-0.846	Destabilizing	0.356	N	0.499	neutral	None	None	None	None	N
V/R	0.1739	likely_benign	0.1704	benign	-0.289	Destabilizing	0.214	N	0.501	neutral	None	None	None	None	N
V/S	0.1038	likely_benign	0.109	benign	-1.052	Destabilizing	0.003	N	0.318	neutral	None	None	None	None	N
V/T	0.0914	likely_benign	0.1051	benign	-1.017	Destabilizing	None	N	0.158	neutral	None	None	None	None	N
V/W	0.712	likely_pathogenic	0.7213	pathogenic	-1.36	Destabilizing	0.864	D	0.501	neutral	None	None	None	None	N
V/Y	0.364	ambiguous	0.379	ambiguous	-1.081	Destabilizing	0.356	N	0.407	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.