TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23373	70342;70343;70344	chr2:178576015;178576014;178576013	chr2:179440742;179440741;179440740
N2AB	21732	65419;65420;65421	chr2:178576015;178576014;178576013	chr2:179440742;179440741;179440740
N2A	20805	62638;62639;62640	chr2:178576015;178576014;178576013	chr2:179440742;179440741;179440740
N2B	14308	43147;43148;43149	chr2:178576015;178576014;178576013	chr2:179440742;179440741;179440740
Novex-1	14433	43522;43523;43524	chr2:178576015;178576014;178576013	chr2:179440742;179440741;179440740
Novex-2	14500	43723;43724;43725	chr2:178576015;178576014;178576013	chr2:179440742;179440741;179440740
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: Ig-129
• Domain position: 29
• Structural Position: 43
• Q(SASA): 0.4756
• 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	0.012	N	0.183	0.143	0.327686398923	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.625E-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
A/C	0.3839	ambiguous	0.4605	ambiguous	-0.667	Destabilizing	0.996	D	0.375	neutral	None	None	None	None	I
A/D	0.3208	likely_benign	0.4045	ambiguous	-0.76	Destabilizing	0.884	D	0.495	neutral	N	0.51375892	None	None	I
A/E	0.2513	likely_benign	0.3106	benign	-0.913	Destabilizing	0.742	D	0.379	neutral	None	None	None	None	I
A/F	0.2551	likely_benign	0.3272	benign	-1.051	Destabilizing	0.02	N	0.348	neutral	None	None	None	None	I
A/G	0.1861	likely_benign	0.2168	benign	-0.553	Destabilizing	0.684	D	0.249	neutral	N	0.485403295	None	None	I
A/H	0.4093	ambiguous	0.4887	ambiguous	-0.713	Destabilizing	0.996	D	0.516	neutral	None	None	None	None	I
A/I	0.1247	likely_benign	0.1587	benign	-0.454	Destabilizing	0.59	D	0.376	neutral	None	None	None	None	I
A/K	0.3803	ambiguous	0.4851	ambiguous	-0.899	Destabilizing	0.742	D	0.376	neutral	None	None	None	None	I
A/L	0.1117	likely_benign	0.1315	benign	-0.454	Destabilizing	0.373	N	0.342	neutral	None	None	None	None	I
A/M	0.1393	likely_benign	0.167	benign	-0.372	Destabilizing	0.953	D	0.407	neutral	None	None	None	None	I
A/N	0.209	likely_benign	0.2551	benign	-0.439	Destabilizing	0.91	D	0.515	neutral	None	None	None	None	I
A/P	0.1039	likely_benign	0.1165	benign	-0.426	Destabilizing	0.007	N	0.275	neutral	N	0.436415645	None	None	I
A/Q	0.27	likely_benign	0.3186	benign	-0.748	Destabilizing	0.953	D	0.409	neutral	None	None	None	None	I
A/R	0.3845	ambiguous	0.4758	ambiguous	-0.406	Destabilizing	0.953	D	0.409	neutral	None	None	None	None	I
A/S	0.0936	likely_benign	0.0976	benign	-0.61	Destabilizing	0.521	D	0.294	neutral	N	0.509950611	None	None	I
A/T	0.0694	likely_benign	0.0752	benign	-0.694	Destabilizing	0.012	N	0.183	neutral	N	0.42898824	None	None	I
A/V	0.0803	likely_benign	0.0935	benign	-0.426	Destabilizing	0.012	N	0.183	neutral	N	0.489460696	None	None	I
A/W	0.6854	likely_pathogenic	0.7699	pathogenic	-1.212	Destabilizing	0.996	D	0.559	neutral	None	None	None	None	I
A/Y	0.3714	ambiguous	0.4662	ambiguous	-0.879	Destabilizing	0.835	D	0.52	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.