TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28074	84445;84446;84447	chr2:178561912;178561911;178561910	chr2:179426639;179426638;179426637
N2AB	26433	79522;79523;79524	chr2:178561912;178561911;178561910	chr2:179426639;179426638;179426637
N2A	25506	76741;76742;76743	chr2:178561912;178561911;178561910	chr2:179426639;179426638;179426637
N2B	19009	57250;57251;57252	chr2:178561912;178561911;178561910	chr2:179426639;179426638;179426637
Novex-1	19134	57625;57626;57627	chr2:178561912;178561911;178561910	chr2:179426639;179426638;179426637
Novex-2	19201	57826;57827;57828	chr2:178561912;178561911;178561910	chr2:179426639;179426638;179426637
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-92
• Domain position: 20
• Structural Position: 22
• Q(SASA): 0.0754
• 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/V	rs1202396763	None	0.022	N	0.224	0.092	0.381409048467	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
I/V	rs1202396763	None	0.022	N	0.224	0.092	0.381409048467	gnomAD-4.0.0	6.57099E-06	None	None	None	None	N	None	2.41243E-05	0	None	0	0	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
I/A	0.8591	likely_pathogenic	0.7691	pathogenic	-2.682	Highly Destabilizing	0.688	D	0.664	neutral	None	None	None	None	N
I/C	0.9094	likely_pathogenic	0.8338	pathogenic	-1.923	Destabilizing	0.998	D	0.781	deleterious	None	None	None	None	N
I/D	0.999	likely_pathogenic	0.9969	pathogenic	-3.142	Highly Destabilizing	0.991	D	0.837	deleterious	None	None	None	None	N
I/E	0.9978	likely_pathogenic	0.9937	pathogenic	-2.8	Highly Destabilizing	0.991	D	0.811	deleterious	None	None	None	None	N
I/F	0.3873	ambiguous	0.2682	benign	-1.634	Destabilizing	0.012	N	0.4	neutral	N	0.477534076	None	None	N
I/G	0.9891	likely_pathogenic	0.9735	pathogenic	-3.316	Highly Destabilizing	0.974	D	0.805	deleterious	None	None	None	None	N
I/H	0.9946	likely_pathogenic	0.9835	pathogenic	-3.127	Highly Destabilizing	0.998	D	0.86	deleterious	None	None	None	None	N
I/K	0.995	likely_pathogenic	0.985	pathogenic	-1.88	Destabilizing	0.974	D	0.812	deleterious	None	None	None	None	N
I/L	0.1118	likely_benign	0.0967	benign	-0.768	Destabilizing	0.002	N	0.199	neutral	N	0.338013079	None	None	N
I/M	0.187	likely_benign	0.1443	benign	-1.047	Destabilizing	0.934	D	0.601	neutral	N	0.48384894	None	None	N
I/N	0.9895	likely_pathogenic	0.9668	pathogenic	-2.617	Highly Destabilizing	0.989	D	0.854	deleterious	N	0.50529957	None	None	N
I/P	0.9963	likely_pathogenic	0.9918	pathogenic	-1.397	Destabilizing	0.991	D	0.85	deleterious	None	None	None	None	N
I/Q	0.9939	likely_pathogenic	0.9833	pathogenic	-2.199	Highly Destabilizing	0.991	D	0.855	deleterious	None	None	None	None	N
I/R	0.9908	likely_pathogenic	0.9739	pathogenic	-2.097	Highly Destabilizing	0.974	D	0.85	deleterious	None	None	None	None	N
I/S	0.9732	likely_pathogenic	0.9312	pathogenic	-3.196	Highly Destabilizing	0.891	D	0.763	deleterious	N	0.50529957	None	None	N
I/T	0.9466	likely_pathogenic	0.881	pathogenic	-2.674	Highly Destabilizing	0.801	D	0.685	prob.neutral	N	0.50504608	None	None	N
I/V	0.0863	likely_benign	0.0799	benign	-1.397	Destabilizing	0.022	N	0.224	neutral	N	0.411095047	None	None	N
I/W	0.9901	likely_pathogenic	0.974	pathogenic	-1.98	Destabilizing	0.998	D	0.855	deleterious	None	None	None	None	N
I/Y	0.9457	likely_pathogenic	0.8732	pathogenic	-1.782	Destabilizing	0.904	D	0.747	deleterious	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.