TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5297	16114;16115;16116	chr2:178733404;178733403;178733402	chr2:179598131;179598130;179598129
N2AB	4980	15163;15164;15165	chr2:178733404;178733403;178733402	chr2:179598131;179598130;179598129
N2A	4053	12382;12383;12384	chr2:178733404;178733403;178733402	chr2:179598131;179598130;179598129
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: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-36
• Domain position: 37
• Structural Position: 51
• Q(SASA): 0.6041
• 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/Y	rs2080895374	None	0.999	D	0.614	0.417	0.689665905704	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	1.92901E-04	None	0	0	0	0	0
D/Y	rs2080895374	None	0.999	D	0.614	0.417	0.689665905704	gnomAD-4.0.0	2.56232E-06	None	None	None	None	I	None	0	0	None	0	2.42483E-05	None	0	0	0	0	2.84446E-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
D/A	0.259	likely_benign	0.3354	benign	-0.612	Destabilizing	0.885	D	0.53	neutral	D	0.610357677	None	None	I
D/C	0.718	likely_pathogenic	0.768	pathogenic	-0.262	Destabilizing	0.999	D	0.626	neutral	None	None	None	None	I
D/E	0.2357	likely_benign	0.3167	benign	-0.441	Destabilizing	0.046	N	0.271	neutral	N	0.519561744	None	None	I
D/F	0.713	likely_pathogenic	0.7928	pathogenic	-0.26	Destabilizing	0.999	D	0.613	neutral	None	None	None	None	I
D/G	0.1722	likely_benign	0.2042	benign	-0.878	Destabilizing	0.046	N	0.347	neutral	N	0.509970307	None	None	I
D/H	0.4513	ambiguous	0.5045	ambiguous	-0.232	Destabilizing	0.998	D	0.52	neutral	D	0.66398163	None	None	I
D/I	0.7012	likely_pathogenic	0.7711	pathogenic	0.069	Stabilizing	0.993	D	0.635	neutral	None	None	None	None	I
D/K	0.6471	likely_pathogenic	0.686	pathogenic	-0.12	Destabilizing	0.973	D	0.509	neutral	None	None	None	None	I
D/L	0.5966	likely_pathogenic	0.6771	pathogenic	0.069	Stabilizing	0.986	D	0.641	neutral	None	None	None	None	I
D/M	0.7592	likely_pathogenic	0.8338	pathogenic	0.298	Stabilizing	0.999	D	0.615	neutral	None	None	None	None	I
D/N	0.1116	likely_benign	0.124	benign	-0.524	Destabilizing	0.982	D	0.482	neutral	N	0.448020626	None	None	I
D/P	0.972	likely_pathogenic	0.9818	pathogenic	-0.135	Destabilizing	0.993	D	0.555	neutral	None	None	None	None	I
D/Q	0.511	ambiguous	0.5925	pathogenic	-0.447	Destabilizing	0.973	D	0.519	neutral	None	None	None	None	I
D/R	0.641	likely_pathogenic	0.6796	pathogenic	0.155	Stabilizing	0.986	D	0.568	neutral	None	None	None	None	I
D/S	0.1956	likely_benign	0.2465	benign	-0.689	Destabilizing	0.953	D	0.473	neutral	None	None	None	None	I
D/T	0.5391	ambiguous	0.6219	pathogenic	-0.474	Destabilizing	0.986	D	0.525	neutral	None	None	None	None	I
D/V	0.464	ambiguous	0.5433	ambiguous	-0.135	Destabilizing	0.991	D	0.648	neutral	D	0.624705653	None	None	I
D/W	0.9067	likely_pathogenic	0.9351	pathogenic	-0.02	Destabilizing	0.999	D	0.615	neutral	None	None	None	None	I
D/Y	0.305	likely_benign	0.343	ambiguous	-0.01	Destabilizing	0.999	D	0.614	neutral	D	0.735468477	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.