TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7766	23521;23522;23523	chr2:178720466;178720465;178720464	chr2:179585193;179585192;179585191
N2AB	7449	22570;22571;22572	chr2:178720466;178720465;178720464	chr2:179585193;179585192;179585191
N2A	6522	19789;19790;19791	chr2:178720466;178720465;178720464	chr2:179585193;179585192;179585191
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: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Ig-62
• Domain position: 65
• Structural Position: 146
• Q(SASA): 0.5072
• 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
A/D	None	None	0.032	N	0.293	0.192	None	gnomAD-4.0.0	2.05281E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99551E-07	0	3.31367E-05

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
A/C	0.5493	ambiguous	0.605	pathogenic	-0.896	Destabilizing	0.998	D	0.35	neutral	None	None	None	None	N
A/D	0.2462	likely_benign	0.3092	benign	-0.325	Destabilizing	0.032	N	0.293	neutral	N	0.492457276	None	None	N
A/E	0.2731	likely_benign	0.3158	benign	-0.392	Destabilizing	0.754	D	0.368	neutral	None	None	None	None	N
A/F	0.2577	likely_benign	0.3008	benign	-0.774	Destabilizing	0.978	D	0.511	neutral	None	None	None	None	N
A/G	0.1037	likely_benign	0.1221	benign	-0.66	Destabilizing	0.698	D	0.343	neutral	N	0.501346118	None	None	N
A/H	0.4303	ambiguous	0.4912	ambiguous	-0.479	Destabilizing	0.998	D	0.522	neutral	None	None	None	None	N
A/I	0.1622	likely_benign	0.1822	benign	-0.247	Destabilizing	0.956	D	0.365	neutral	None	None	None	None	N
A/K	0.4974	ambiguous	0.5576	ambiguous	-0.701	Destabilizing	0.86	D	0.339	neutral	None	None	None	None	N
A/L	0.1333	likely_benign	0.1519	benign	-0.247	Destabilizing	0.86	D	0.354	neutral	None	None	None	None	N
A/M	0.1668	likely_benign	0.1896	benign	-0.52	Destabilizing	0.998	D	0.403	neutral	None	None	None	None	N
A/N	0.16	likely_benign	0.1963	benign	-0.513	Destabilizing	0.915	D	0.449	neutral	None	None	None	None	N
A/P	0.104	likely_benign	0.1201	benign	-0.295	Destabilizing	0.97	D	0.369	neutral	N	0.446548841	None	None	N
A/Q	0.3241	likely_benign	0.3716	ambiguous	-0.646	Destabilizing	0.956	D	0.354	neutral	None	None	None	None	N
A/R	0.5118	ambiguous	0.5666	pathogenic	-0.338	Destabilizing	0.956	D	0.361	neutral	None	None	None	None	N
A/S	0.0776	likely_benign	0.0877	benign	-0.847	Destabilizing	0.058	N	0.227	neutral	N	0.446780914	None	None	N
A/T	0.0762	likely_benign	0.0824	benign	-0.801	Destabilizing	0.058	N	0.287	neutral	N	0.467790904	None	None	N
A/V	0.0951	likely_benign	0.1041	benign	-0.295	Destabilizing	0.822	D	0.328	neutral	N	0.455515041	None	None	N
A/W	0.6771	likely_pathogenic	0.7259	pathogenic	-0.962	Destabilizing	0.998	D	0.649	neutral	None	None	None	None	N
A/Y	0.3892	ambiguous	0.4377	ambiguous	-0.592	Destabilizing	0.993	D	0.503	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.