TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30567	91924;91925;91926	chr2:178550139;178550138;178550137	chr2:179414866;179414865;179414864
N2AB	28926	87001;87002;87003	chr2:178550139;178550138;178550137	chr2:179414866;179414865;179414864
N2A	27999	84220;84221;84222	chr2:178550139;178550138;178550137	chr2:179414866;179414865;179414864
N2B	21502	64729;64730;64731	chr2:178550139;178550138;178550137	chr2:179414866;179414865;179414864
Novex-1	21627	65104;65105;65106	chr2:178550139;178550138;178550137	chr2:179414866;179414865;179414864
Novex-2	21694	65305;65306;65307	chr2:178550139;178550138;178550137	chr2:179414866;179414865;179414864
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-149
• Domain position: 36
• Structural Position: 58
• Q(SASA): 0.1624
• Predicted PPI site: N

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
I/T	rs1472322542	-2.775	0.822	N	0.587	0.575	0.771135475104	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
I/T	rs1472322542	-2.775	0.822	N	0.587	0.575	0.771135475104	gnomAD-4.0.0	1.59126E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85837E-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
I/A	0.4166	ambiguous	0.4136	ambiguous	-2.454	Highly Destabilizing	0.717	D	0.554	neutral	None	None	None	None	N
I/C	0.8311	likely_pathogenic	0.811	pathogenic	-1.593	Destabilizing	0.998	D	0.651	neutral	None	None	None	None	N
I/D	0.9598	likely_pathogenic	0.9532	pathogenic	-2.774	Highly Destabilizing	0.993	D	0.748	deleterious	None	None	None	None	N
I/E	0.8955	likely_pathogenic	0.8805	pathogenic	-2.592	Highly Destabilizing	0.978	D	0.722	prob.delet.	None	None	None	None	N
I/F	0.2519	likely_benign	0.2383	benign	-1.522	Destabilizing	0.942	D	0.577	neutral	N	0.509044639	None	None	N
I/G	0.8701	likely_pathogenic	0.8604	pathogenic	-2.928	Highly Destabilizing	0.978	D	0.711	prob.delet.	None	None	None	None	N
I/H	0.8981	likely_pathogenic	0.8805	pathogenic	-2.167	Highly Destabilizing	0.998	D	0.735	prob.delet.	None	None	None	None	N
I/K	0.8582	likely_pathogenic	0.8387	pathogenic	-2.084	Highly Destabilizing	0.978	D	0.72	prob.delet.	None	None	None	None	N
I/L	0.1146	likely_benign	0.1049	benign	-1.106	Destabilizing	0.006	N	0.231	neutral	N	0.447320498	None	None	N
I/M	0.0918	likely_benign	0.0851	benign	-0.887	Destabilizing	0.976	D	0.591	neutral	N	0.492332736	None	None	N
I/N	0.761	likely_pathogenic	0.7178	pathogenic	-2.304	Highly Destabilizing	0.99	D	0.753	deleterious	N	0.517464884	None	None	N
I/P	0.9307	likely_pathogenic	0.9368	pathogenic	-1.536	Destabilizing	0.993	D	0.749	deleterious	None	None	None	None	N
I/Q	0.8514	likely_pathogenic	0.8283	pathogenic	-2.272	Highly Destabilizing	0.993	D	0.749	deleterious	None	None	None	None	N
I/R	0.7978	likely_pathogenic	0.7721	pathogenic	-1.621	Destabilizing	0.978	D	0.752	deleterious	None	None	None	None	N
I/S	0.6739	likely_pathogenic	0.6396	pathogenic	-2.915	Highly Destabilizing	0.97	D	0.656	neutral	D	0.526174616	None	None	N
I/T	0.31	likely_benign	0.3037	benign	-2.599	Highly Destabilizing	0.822	D	0.587	neutral	N	0.51976538	None	None	N
I/V	0.0918	likely_benign	0.0938	benign	-1.536	Destabilizing	0.025	N	0.203	neutral	N	0.487191182	None	None	N
I/W	0.8766	likely_pathogenic	0.8582	pathogenic	-1.823	Destabilizing	0.998	D	0.73	prob.delet.	None	None	None	None	N
I/Y	0.7501	likely_pathogenic	0.7051	pathogenic	-1.552	Destabilizing	0.978	D	0.687	prob.neutral	None	None	None	None	N

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.