TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21446	64561;64562;64563	chr2:178586565;178586564;178586563	chr2:179451292;179451291;179451290
N2AB	19805	59638;59639;59640	chr2:178586565;178586564;178586563	chr2:179451292;179451291;179451290
N2A	18878	56857;56858;56859	chr2:178586565;178586564;178586563	chr2:179451292;179451291;179451290
N2B	12381	37366;37367;37368	chr2:178586565;178586564;178586563	chr2:179451292;179451291;179451290
Novex-1	12506	37741;37742;37743	chr2:178586565;178586564;178586563	chr2:179451292;179451291;179451290
Novex-2	12573	37942;37943;37944	chr2:178586565;178586564;178586563	chr2:179451292;179451291;179451290
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Fn3-43
• Domain position: 81
• Structural Position: 113
• Q(SASA): 0.5936
• Predicted PPI site: I

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/V	None	None	0.645	N	0.358	0.218	0.455909487837	gnomAD-4.0.0	1.59252E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.4332E-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
A/C	0.4805	ambiguous	0.463	ambiguous	-0.709	Destabilizing	0.985	D	0.357	neutral	None	None	None	None	I
A/D	0.3857	ambiguous	0.3397	benign	-0.581	Destabilizing	0.864	D	0.455	neutral	N	0.459433285	None	None	I
A/E	0.2981	likely_benign	0.2647	benign	-0.747	Destabilizing	0.547	D	0.389	neutral	None	None	None	None	I
A/F	0.4466	ambiguous	0.409	ambiguous	-0.915	Destabilizing	0.945	D	0.578	neutral	None	None	None	None	I
A/G	0.1755	likely_benign	0.1713	benign	-0.224	Destabilizing	0.273	N	0.392	neutral	N	0.480419059	None	None	I
A/H	0.4434	ambiguous	0.4097	ambiguous	-0.246	Destabilizing	0.985	D	0.561	neutral	None	None	None	None	I
A/I	0.2167	likely_benign	0.2011	benign	-0.347	Destabilizing	0.894	D	0.418	neutral	None	None	None	None	I
A/K	0.4297	ambiguous	0.3699	ambiguous	-0.549	Destabilizing	0.547	D	0.385	neutral	None	None	None	None	I
A/L	0.1841	likely_benign	0.1665	benign	-0.347	Destabilizing	0.707	D	0.412	neutral	None	None	None	None	I
A/M	0.2264	likely_benign	0.212	benign	-0.363	Destabilizing	0.995	D	0.415	neutral	None	None	None	None	I
A/N	0.2427	likely_benign	0.2322	benign	-0.213	Destabilizing	0.809	D	0.462	neutral	None	None	None	None	I
A/P	0.2692	likely_benign	0.2353	benign	-0.268	Destabilizing	0.928	D	0.42	neutral	N	0.48479309	None	None	I
A/Q	0.3168	likely_benign	0.2861	benign	-0.529	Destabilizing	0.894	D	0.412	neutral	None	None	None	None	I
A/R	0.4175	ambiguous	0.3543	ambiguous	-0.047	Destabilizing	0.894	D	0.416	neutral	None	None	None	None	I
A/S	0.0985	likely_benign	0.1	benign	-0.378	Destabilizing	0.002	N	0.251	neutral	N	0.408255103	None	None	I
A/T	0.091	likely_benign	0.092	benign	-0.472	Destabilizing	0.477	N	0.356	neutral	N	0.485579736	None	None	I
A/V	0.1203	likely_benign	0.1146	benign	-0.268	Destabilizing	0.645	D	0.358	neutral	N	0.477731044	None	None	I
A/W	0.7897	likely_pathogenic	0.7316	pathogenic	-1.032	Destabilizing	0.995	D	0.688	prob.neutral	None	None	None	None	I
A/Y	0.5513	ambiguous	0.5012	ambiguous	-0.688	Destabilizing	0.981	D	0.569	neutral	None	None	None	None	I

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.