TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18471	55636;55637;55638	chr2:178601679;178601678;178601677	chr2:179466406;179466405;179466404
N2AB	16830	50713;50714;50715	chr2:178601679;178601678;178601677	chr2:179466406;179466405;179466404
N2A	15903	47932;47933;47934	chr2:178601679;178601678;178601677	chr2:179466406;179466405;179466404
N2B	9406	28441;28442;28443	chr2:178601679;178601678;178601677	chr2:179466406;179466405;179466404
Novex-1	9531	28816;28817;28818	chr2:178601679;178601678;178601677	chr2:179466406;179466405;179466404
Novex-2	9598	29017;29018;29019	chr2:178601679;178601678;178601677	chr2:179466406;179466405;179466404
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-115
• Domain position: 90
• Structural Position: 171
• Q(SASA): 0.52
• 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
N/D	None	None	0.722	N	0.563	0.198	0.18274738541	gnomAD-4.0.0	1.62081E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.88507E-06	0	0
N/I	None	None	0.949	N	0.8	0.325	0.590905048371	gnomAD-4.0.0	4.87824E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.66852E-06	0	0
N/S	rs1310909549	0.045	0.034	N	0.366	0.101	0.101711395817	gnomAD-2.1.1	1.7E-05	None	None	None	None	N	None	0	0	None	0	2.35599E-04	None	0	None	0	0	0
N/S	rs1310909549	0.045	0.034	N	0.366	0.101	0.101711395817	gnomAD-4.0.0	1.62608E-06	None	None	None	None	N	None	0	0	None	0	2.78489E-05	None	0	0	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
N/A	0.1713	likely_benign	0.1564	benign	-0.356	Destabilizing	0.633	D	0.728	prob.delet.	None	None	None	None	N
N/C	0.1943	likely_benign	0.178	benign	0.447	Stabilizing	0.996	D	0.786	deleterious	None	None	None	None	N
N/D	0.2205	likely_benign	0.21	benign	-0.15	Destabilizing	0.722	D	0.563	neutral	N	0.483398728	None	None	N
N/E	0.4798	ambiguous	0.4423	ambiguous	-0.194	Destabilizing	0.775	D	0.542	neutral	None	None	None	None	N
N/F	0.3021	likely_benign	0.2656	benign	-0.752	Destabilizing	0.923	D	0.8	deleterious	None	None	None	None	N
N/G	0.2516	likely_benign	0.2272	benign	-0.523	Destabilizing	0.633	D	0.559	neutral	None	None	None	None	N
N/H	0.0807	likely_benign	0.0826	benign	-0.627	Destabilizing	0.008	N	0.36	neutral	N	0.500600409	None	None	N
N/I	0.1395	likely_benign	0.1215	benign	-0.002	Destabilizing	0.949	D	0.8	deleterious	N	0.490403271	None	None	N
N/K	0.4193	ambiguous	0.3814	ambiguous	0.077	Stabilizing	0.565	D	0.581	neutral	N	0.479067557	None	None	N
N/L	0.1788	likely_benign	0.1538	benign	-0.002	Destabilizing	0.923	D	0.755	deleterious	None	None	None	None	N
N/M	0.2643	likely_benign	0.2273	benign	0.499	Stabilizing	0.996	D	0.785	deleterious	None	None	None	None	N
N/P	0.569	likely_pathogenic	0.5679	pathogenic	-0.094	Destabilizing	0.961	D	0.802	deleterious	None	None	None	None	N
N/Q	0.3213	likely_benign	0.2935	benign	-0.39	Destabilizing	0.923	D	0.609	neutral	None	None	None	None	N
N/R	0.4165	ambiguous	0.3932	ambiguous	0.168	Stabilizing	0.923	D	0.596	neutral	None	None	None	None	N
N/S	0.0664	likely_benign	0.0627	benign	-0.086	Destabilizing	0.034	N	0.366	neutral	N	0.435951498	None	None	N
N/T	0.0945	likely_benign	0.0864	benign	0.002	Stabilizing	0.565	D	0.573	neutral	N	0.480107707	None	None	N
N/V	0.1403	likely_benign	0.125	benign	-0.094	Destabilizing	0.923	D	0.789	deleterious	None	None	None	None	N
N/W	0.6143	likely_pathogenic	0.5735	pathogenic	-0.736	Destabilizing	0.996	D	0.721	prob.delet.	None	None	None	None	N
N/Y	0.1089	likely_benign	0.1025	benign	-0.473	Destabilizing	0.82	D	0.804	deleterious	D	0.530749958	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.