TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30912	92959;92960;92961	chr2:178548892;178548891;178548890	chr2:179413619;179413618;179413617
N2AB	29271	88036;88037;88038	chr2:178548892;178548891;178548890	chr2:179413619;179413618;179413617
N2A	28344	85255;85256;85257	chr2:178548892;178548891;178548890	chr2:179413619;179413618;179413617
N2B	21847	65764;65765;65766	chr2:178548892;178548891;178548890	chr2:179413619;179413618;179413617
Novex-1	21972	66139;66140;66141	chr2:178548892;178548891;178548890	chr2:179413619;179413618;179413617
Novex-2	22039	66340;66341;66342	chr2:178548892;178548891;178548890	chr2:179413619;179413618;179413617
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Fn3-113
• Domain position: 92
• Structural Position: 125
• Q(SASA): 0.3617
• 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
G/S	rs1698262497	None	0.068	N	0.107	0.135	0.0716867268079	gnomAD-4.0.0	3.18261E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71595E-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
G/A	0.1127	likely_benign	0.1186	benign	-0.265	Destabilizing	0.002	N	0.042	neutral	N	0.473271295	None	None	N
G/C	0.2511	likely_benign	0.2666	benign	-0.974	Destabilizing	0.98	D	0.597	neutral	N	0.470425327	None	None	N
G/D	0.1438	likely_benign	0.1456	benign	-0.566	Destabilizing	0.483	N	0.448	neutral	N	0.429789877	None	None	N
G/E	0.1666	likely_benign	0.1658	benign	-0.719	Destabilizing	0.712	D	0.467	neutral	None	None	None	None	N
G/F	0.641	likely_pathogenic	0.665	pathogenic	-0.927	Destabilizing	0.946	D	0.668	prob.neutral	None	None	None	None	N
G/H	0.3746	ambiguous	0.3871	ambiguous	-0.455	Destabilizing	0.018	N	0.401	neutral	None	None	None	None	N
G/I	0.3685	ambiguous	0.3925	ambiguous	-0.402	Destabilizing	0.897	D	0.611	neutral	None	None	None	None	N
G/K	0.3704	ambiguous	0.3843	ambiguous	-0.863	Destabilizing	0.712	D	0.432	neutral	None	None	None	None	N
G/L	0.4467	ambiguous	0.4618	ambiguous	-0.402	Destabilizing	0.712	D	0.511	neutral	None	None	None	None	N
G/M	0.465	ambiguous	0.4858	ambiguous	-0.574	Destabilizing	0.995	D	0.592	neutral	None	None	None	None	N
G/N	0.1931	likely_benign	0.1984	benign	-0.562	Destabilizing	0.032	N	0.141	neutral	None	None	None	None	N
G/P	0.6464	likely_pathogenic	0.6909	pathogenic	-0.324	Destabilizing	0.946	D	0.495	neutral	None	None	None	None	N
G/Q	0.2901	likely_benign	0.298	benign	-0.817	Destabilizing	0.946	D	0.476	neutral	None	None	None	None	N
G/R	0.2999	likely_benign	0.3167	benign	-0.428	Destabilizing	0.868	D	0.492	neutral	N	0.486104519	None	None	N
G/S	0.0863	likely_benign	0.0891	benign	-0.704	Destabilizing	0.068	N	0.107	neutral	N	0.494665288	None	None	N
G/T	0.133	likely_benign	0.1402	benign	-0.784	Destabilizing	0.553	D	0.425	neutral	None	None	None	None	N
G/V	0.2248	likely_benign	0.2377	benign	-0.324	Destabilizing	0.483	N	0.561	neutral	N	0.491163623	None	None	N
G/W	0.5124	ambiguous	0.5425	ambiguous	-1.086	Destabilizing	0.995	D	0.583	neutral	None	None	None	None	N
G/Y	0.472	ambiguous	0.4914	ambiguous	-0.745	Destabilizing	0.897	D	0.645	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.