TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25524	76795;76796;76797	chr2:178569562;178569561;178569560	chr2:179434289;179434288;179434287
N2AB	23883	71872;71873;71874	chr2:178569562;178569561;178569560	chr2:179434289;179434288;179434287
N2A	22956	69091;69092;69093	chr2:178569562;178569561;178569560	chr2:179434289;179434288;179434287
N2B	16459	49600;49601;49602	chr2:178569562;178569561;178569560	chr2:179434289;179434288;179434287
Novex-1	16584	49975;49976;49977	chr2:178569562;178569561;178569560	chr2:179434289;179434288;179434287
Novex-2	16651	50176;50177;50178	chr2:178569562;178569561;178569560	chr2:179434289;179434288;179434287
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-135
• Domain position: 11
• Structural Position: 23
• Q(SASA): 0.5036
• 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/T	rs766397845	-0.622	0.996	N	0.636	0.217	0.148003135375	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	0	None	0	5.63E-05	None	0	None	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
A/C	0.6828	likely_pathogenic	0.6935	pathogenic	-0.851	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	I
A/D	0.9065	likely_pathogenic	0.9223	pathogenic	-0.733	Destabilizing	0.999	D	0.754	deleterious	None	None	None	None	I
A/E	0.8444	likely_pathogenic	0.8692	pathogenic	-0.874	Destabilizing	0.999	D	0.69	prob.neutral	N	0.487469956	None	None	I
A/F	0.8262	likely_pathogenic	0.8375	pathogenic	-1.043	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	I
A/G	0.3814	ambiguous	0.3899	ambiguous	-0.659	Destabilizing	0.996	D	0.517	neutral	N	0.512361964	None	None	I
A/H	0.8503	likely_pathogenic	0.8654	pathogenic	-0.667	Destabilizing	1.0	D	0.758	deleterious	None	None	None	None	I
A/I	0.7883	likely_pathogenic	0.8032	pathogenic	-0.501	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	I
A/K	0.9278	likely_pathogenic	0.9484	pathogenic	-0.925	Destabilizing	0.999	D	0.695	prob.neutral	None	None	None	None	I
A/L	0.7194	likely_pathogenic	0.7323	pathogenic	-0.501	Destabilizing	0.998	D	0.675	neutral	None	None	None	None	I
A/M	0.7175	likely_pathogenic	0.7211	pathogenic	-0.441	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	I
A/N	0.7428	likely_pathogenic	0.746	pathogenic	-0.572	Destabilizing	0.999	D	0.754	deleterious	None	None	None	None	I
A/P	0.931	likely_pathogenic	0.9438	pathogenic	-0.486	Destabilizing	1.0	D	0.717	prob.delet.	N	0.471594323	None	None	I
A/Q	0.7822	likely_pathogenic	0.7975	pathogenic	-0.874	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	I
A/R	0.8623	likely_pathogenic	0.8928	pathogenic	-0.403	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	I
A/S	0.1502	likely_benign	0.1446	benign	-0.801	Destabilizing	0.957	D	0.416	neutral	N	0.513717982	None	None	I
A/T	0.4483	ambiguous	0.4487	ambiguous	-0.865	Destabilizing	0.996	D	0.636	neutral	N	0.510851035	None	None	I
A/V	0.4489	ambiguous	0.4764	ambiguous	-0.486	Destabilizing	0.998	D	0.688	prob.neutral	N	0.510925606	None	None	I
A/W	0.9672	likely_pathogenic	0.9735	pathogenic	-1.181	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	I
A/Y	0.8749	likely_pathogenic	0.8859	pathogenic	-0.851	Destabilizing	1.0	D	0.777	deleterious	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.