TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32166	96721;96722;96723	chr2:178543477;178543476;178543475	chr2:179408204;179408203;179408202
N2AB	30525	91798;91799;91800	chr2:178543477;178543476;178543475	chr2:179408204;179408203;179408202
N2A	29598	89017;89018;89019	chr2:178543477;178543476;178543475	chr2:179408204;179408203;179408202
N2B	23101	69526;69527;69528	chr2:178543477;178543476;178543475	chr2:179408204;179408203;179408202
Novex-1	23226	69901;69902;69903	chr2:178543477;178543476;178543475	chr2:179408204;179408203;179408202
Novex-2	23293	70102;70103;70104	chr2:178543477;178543476;178543475	chr2:179408204;179408203;179408202
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: Fn3-122
• Domain position: 62
• Structural Position: 93
• Q(SASA): 0.0827
• 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	rs746467659	-1.091	0.006	N	0.185	0.056	0.485275477626	gnomAD-2.1.1	2.15E-05	None	None	None	None	N	None	0	0	None	0	3.08261E-04	None	0	None	0	0	0
I/V	rs746467659	-1.091	0.006	N	0.185	0.056	0.485275477626	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	1.92456E-04	None	0	0	0	0	0
I/V	rs746467659	-1.091	0.006	N	0.185	0.056	0.485275477626	gnomAD-4.0.0	2.5622E-06	None	None	None	None	N	None	0	0	None	0	4.85084E-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
I/A	0.9066	likely_pathogenic	0.8927	pathogenic	-2.196	Highly Destabilizing	0.754	D	0.732	prob.delet.	None	None	None	None	N
I/C	0.9037	likely_pathogenic	0.8895	pathogenic	-1.506	Destabilizing	0.994	D	0.751	deleterious	None	None	None	None	N
I/D	0.9959	likely_pathogenic	0.9948	pathogenic	-2.651	Highly Destabilizing	0.993	D	0.852	deleterious	None	None	None	None	N
I/E	0.9895	likely_pathogenic	0.9878	pathogenic	-2.333	Highly Destabilizing	0.978	D	0.853	deleterious	None	None	None	None	N
I/F	0.4691	ambiguous	0.4427	ambiguous	-1.316	Destabilizing	0.942	D	0.743	deleterious	N	0.471724406	None	None	N
I/G	0.986	likely_pathogenic	0.9837	pathogenic	-2.811	Highly Destabilizing	0.978	D	0.848	deleterious	None	None	None	None	N
I/H	0.9821	likely_pathogenic	0.9791	pathogenic	-2.589	Highly Destabilizing	0.998	D	0.836	deleterious	None	None	None	None	N
I/K	0.9849	likely_pathogenic	0.9835	pathogenic	-1.6	Destabilizing	0.978	D	0.852	deleterious	None	None	None	None	N
I/L	0.2492	likely_benign	0.2371	benign	-0.376	Destabilizing	0.294	N	0.403	neutral	N	0.498370101	None	None	N
I/M	0.347	ambiguous	0.3305	benign	-0.515	Destabilizing	0.942	D	0.713	prob.delet.	N	0.493124025	None	None	N
I/N	0.9572	likely_pathogenic	0.9508	pathogenic	-2.243	Highly Destabilizing	0.99	D	0.85	deleterious	N	0.516343615	None	None	N
I/P	0.9859	likely_pathogenic	0.983	pathogenic	-0.969	Destabilizing	0.993	D	0.849	deleterious	None	None	None	None	N
I/Q	0.9821	likely_pathogenic	0.9806	pathogenic	-1.873	Destabilizing	0.993	D	0.863	deleterious	None	None	None	None	N
I/R	0.9804	likely_pathogenic	0.9775	pathogenic	-1.789	Destabilizing	0.978	D	0.856	deleterious	None	None	None	None	N
I/S	0.9518	likely_pathogenic	0.944	pathogenic	-2.879	Highly Destabilizing	0.942	D	0.811	deleterious	N	0.515836636	None	None	N
I/T	0.9368	likely_pathogenic	0.9293	pathogenic	-2.381	Highly Destabilizing	0.822	D	0.756	deleterious	N	0.498150454	None	None	N
I/V	0.1117	likely_benign	0.1083	benign	-0.969	Destabilizing	0.006	N	0.185	neutral	N	0.431185104	None	None	N
I/W	0.9871	likely_pathogenic	0.982	pathogenic	-1.718	Destabilizing	0.998	D	0.813	deleterious	None	None	None	None	N
I/Y	0.9281	likely_pathogenic	0.9159	pathogenic	-1.386	Destabilizing	0.978	D	0.771	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.