TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24149	72670;72671;72672	chr2:178573687;178573686;178573685	chr2:179438414;179438413;179438412
N2AB	22508	67747;67748;67749	chr2:178573687;178573686;178573685	chr2:179438414;179438413;179438412
N2A	21581	64966;64967;64968	chr2:178573687;178573686;178573685	chr2:179438414;179438413;179438412
N2B	15084	45475;45476;45477	chr2:178573687;178573686;178573685	chr2:179438414;179438413;179438412
Novex-1	15209	45850;45851;45852	chr2:178573687;178573686;178573685	chr2:179438414;179438413;179438412
Novex-2	15276	46051;46052;46053	chr2:178573687;178573686;178573685	chr2:179438414;179438413;179438412
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-63
• Domain position: 28
• Structural Position: 29
• Q(SASA): 0.7896
• 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
D/H	None	None	0.005	N	0.161	0.127	0.225902525712	gnomAD-4.0.0	1.8644E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	2.69833E-04	0	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
D/A	0.3679	ambiguous	0.4295	ambiguous	-0.424	Destabilizing	0.669	D	0.467	neutral	N	0.469354095	None	None	I
D/C	0.7641	likely_pathogenic	0.8046	pathogenic	0.033	Stabilizing	0.998	D	0.5	neutral	None	None	None	None	I
D/E	0.2299	likely_benign	0.3044	benign	-0.398	Destabilizing	0.625	D	0.422	neutral	N	0.449696294	None	None	I
D/F	0.7196	likely_pathogenic	0.7619	pathogenic	-0.374	Destabilizing	0.974	D	0.493	neutral	None	None	None	None	I
D/G	0.4648	ambiguous	0.5226	ambiguous	-0.643	Destabilizing	0.801	D	0.449	neutral	N	0.473811093	None	None	I
D/H	0.3618	ambiguous	0.4482	ambiguous	-0.412	Destabilizing	0.005	N	0.161	neutral	N	0.473554589	None	None	I
D/I	0.6362	likely_pathogenic	0.6863	pathogenic	0.109	Stabilizing	0.974	D	0.501	neutral	None	None	None	None	I
D/K	0.7182	likely_pathogenic	0.7862	pathogenic	0.16	Stabilizing	0.842	D	0.481	neutral	None	None	None	None	I
D/L	0.555	ambiguous	0.6277	pathogenic	0.109	Stabilizing	0.949	D	0.478	neutral	None	None	None	None	I
D/M	0.7702	likely_pathogenic	0.8123	pathogenic	0.395	Stabilizing	0.998	D	0.465	neutral	None	None	None	None	I
D/N	0.1839	likely_benign	0.193	benign	-0.15	Destabilizing	0.801	D	0.457	neutral	N	0.481403281	None	None	I
D/P	0.9625	likely_pathogenic	0.9705	pathogenic	-0.046	Destabilizing	0.974	D	0.425	neutral	None	None	None	None	I
D/Q	0.4763	ambiguous	0.5708	pathogenic	-0.099	Destabilizing	0.949	D	0.369	neutral	None	None	None	None	I
D/R	0.6989	likely_pathogenic	0.7654	pathogenic	0.253	Stabilizing	0.949	D	0.465	neutral	None	None	None	None	I
D/S	0.2681	likely_benign	0.2994	benign	-0.256	Destabilizing	0.172	N	0.197	neutral	None	None	None	None	I
D/T	0.5118	ambiguous	0.5694	pathogenic	-0.084	Destabilizing	0.728	D	0.483	neutral	None	None	None	None	I
D/V	0.4247	ambiguous	0.4749	ambiguous	-0.046	Destabilizing	0.966	D	0.477	neutral	N	0.4807104	None	None	I
D/W	0.9284	likely_pathogenic	0.943	pathogenic	-0.236	Destabilizing	0.998	D	0.588	neutral	None	None	None	None	I
D/Y	0.3686	ambiguous	0.4338	ambiguous	-0.146	Destabilizing	0.934	D	0.491	neutral	N	0.495642014	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.