TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16834	50725;50726;50727	chr2:178611809;178611808;178611807	chr2:179476536;179476535;179476534
N2AB	15193	45802;45803;45804	chr2:178611809;178611808;178611807	chr2:179476536;179476535;179476534
N2A	14266	43021;43022;43023	chr2:178611809;178611808;178611807	chr2:179476536;179476535;179476534
N2B	7769	23530;23531;23532	chr2:178611809;178611808;178611807	chr2:179476536;179476535;179476534
Novex-1	7894	23905;23906;23907	chr2:178611809;178611808;178611807	chr2:179476536;179476535;179476534
Novex-2	7961	24106;24107;24108	chr2:178611809;178611808;178611807	chr2:179476536;179476535;179476534
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-10
• Domain position: 84
• Structural Position: 116
• Q(SASA): 0.3683
• 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	None	None	0.027	N	0.471	0.06	0.317084106153	gnomAD-4.0.0	1.59328E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86171E-06	0	0
V/I	None	None	None	N	0.217	0.051	0.262662153117	gnomAD-4.0.0	4.80129E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.9375E-06	6.07533E-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
V/A	0.2503	likely_benign	0.3228	benign	-1.09	Destabilizing	0.027	N	0.471	neutral	N	0.475720943	None	None	N
V/C	0.724	likely_pathogenic	0.709	pathogenic	-0.858	Destabilizing	0.001	N	0.351	neutral	None	None	None	None	N
V/D	0.7311	likely_pathogenic	0.8223	pathogenic	-0.877	Destabilizing	0.317	N	0.693	prob.neutral	N	0.512208731	None	None	N
V/E	0.6109	likely_pathogenic	0.7248	pathogenic	-0.966	Destabilizing	0.555	D	0.689	prob.neutral	None	None	None	None	N
V/F	0.2476	likely_benign	0.3322	benign	-1.158	Destabilizing	0.317	N	0.643	neutral	N	0.495942242	None	None	N
V/G	0.4151	ambiguous	0.5143	ambiguous	-1.29	Destabilizing	None	N	0.498	neutral	D	0.534410464	None	None	N
V/H	0.8164	likely_pathogenic	0.8811	pathogenic	-0.733	Destabilizing	0.935	D	0.687	prob.neutral	None	None	None	None	N
V/I	0.0794	likely_benign	0.0864	benign	-0.684	Destabilizing	None	N	0.217	neutral	N	0.469351893	None	None	N
V/K	0.7609	likely_pathogenic	0.823	pathogenic	-0.753	Destabilizing	0.38	N	0.681	prob.neutral	None	None	None	None	N
V/L	0.2945	likely_benign	0.3661	ambiguous	-0.684	Destabilizing	0.009	N	0.408	neutral	N	0.464043847	None	None	N
V/M	0.2062	likely_benign	0.2653	benign	-0.498	Destabilizing	0.38	N	0.629	neutral	None	None	None	None	N
V/N	0.4956	ambiguous	0.6245	pathogenic	-0.48	Destabilizing	0.38	N	0.696	prob.neutral	None	None	None	None	N
V/P	0.7537	likely_pathogenic	0.7561	pathogenic	-0.784	Destabilizing	0.555	D	0.689	prob.neutral	None	None	None	None	N
V/Q	0.6069	likely_pathogenic	0.6982	pathogenic	-0.794	Destabilizing	0.555	D	0.685	prob.neutral	None	None	None	None	N
V/R	0.6954	likely_pathogenic	0.7584	pathogenic	-0.141	Destabilizing	0.555	D	0.695	prob.neutral	None	None	None	None	N
V/S	0.3378	likely_benign	0.4429	ambiguous	-0.93	Destabilizing	0.081	N	0.665	neutral	None	None	None	None	N
V/T	0.2201	likely_benign	0.2874	benign	-0.919	Destabilizing	0.149	N	0.509	neutral	None	None	None	None	N
V/W	0.9034	likely_pathogenic	0.9342	pathogenic	-1.186	Destabilizing	0.935	D	0.695	prob.neutral	None	None	None	None	N
V/Y	0.7302	likely_pathogenic	0.7891	pathogenic	-0.904	Destabilizing	0.555	D	0.623	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.