TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34199	102820;102821;102822	chr2:178534020;178534019;178534018	chr2:179398747;179398746;179398745
N2AB	32558	97897;97898;97899	chr2:178534020;178534019;178534018	chr2:179398747;179398746;179398745
N2A	31631	95116;95117;95118	chr2:178534020;178534019;178534018	chr2:179398747;179398746;179398745
N2B	25134	75625;75626;75627	chr2:178534020;178534019;178534018	chr2:179398747;179398746;179398745
Novex-1	25259	76000;76001;76002	chr2:178534020;178534019;178534018	chr2:179398747;179398746;179398745
Novex-2	25326	76201;76202;76203	chr2:178534020;178534019;178534018	chr2:179398747;179398746;179398745
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: Ig-160
• Domain position: 63
• Structural Position: 144
• Q(SASA): 0.0849
• 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/M	rs749009190	-1.193	0.968	D	0.605	0.444	0.564429724435	gnomAD-2.1.1	4.01E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	4.64E-05	0	0
I/M	rs749009190	-1.193	0.968	D	0.605	0.444	0.564429724435	gnomAD-4.0.0	3.182E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.76605E-05	0	0	0	0
I/V	rs56347248	-1.471	0.437	N	0.453	0.126	None	gnomAD-2.1.1	3.38351E-03	None	None	None	None	N	None	1.23967E-04	7.63964E-04	None	1.0626E-03	0	None	2.17334E-02	None	4E-05	1.72247E-03	2.94118E-03
I/V	rs56347248	-1.471	0.437	N	0.453	0.126	None	gnomAD-3.1.2	1.72112E-03	None	None	None	None	N	None	1.68789E-04	1.6357E-03	0	8.64055E-04	0	None	0	0	1.64628E-03	2.31884E-02	1.43541E-03
I/V	rs56347248	-1.471	0.437	N	0.453	0.126	None	1000 genomes	5.99042E-03	None	None	None	None	N	None	0	1.4E-03	None	None	0	2E-03	None	None	None	2.76E-02	None
I/V	rs56347248	-1.471	0.437	N	0.453	0.126	None	gnomAD-4.0.0	2.16048E-03	None	None	None	None	N	None	2.39783E-04	9.33022E-04	None	8.44423E-04	4.45593E-05	None	6.2498E-05	4.12405E-03	1.06368E-03	2.12336E-02	2.6886E-03

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	0.7835	likely_pathogenic	0.859	pathogenic	-2.207	Highly Destabilizing	0.702	D	0.564	neutral	None	None	None	None	N
I/C	0.9117	likely_pathogenic	0.9387	pathogenic	-1.887	Destabilizing	0.076	N	0.499	neutral	None	None	None	None	N
I/D	0.9842	likely_pathogenic	0.9908	pathogenic	-2.633	Highly Destabilizing	0.996	D	0.707	prob.neutral	None	None	None	None	N
I/E	0.9709	likely_pathogenic	0.9813	pathogenic	-2.584	Highly Destabilizing	0.996	D	0.705	prob.neutral	None	None	None	None	N
I/F	0.5983	likely_pathogenic	0.6794	pathogenic	-1.654	Destabilizing	0.968	D	0.651	neutral	N	0.489966106	None	None	N
I/G	0.9695	likely_pathogenic	0.9817	pathogenic	-2.576	Highly Destabilizing	0.988	D	0.688	prob.neutral	None	None	None	None	N
I/H	0.963	likely_pathogenic	0.9795	pathogenic	-1.736	Destabilizing	0.999	D	0.684	prob.neutral	None	None	None	None	N
I/K	0.9194	likely_pathogenic	0.9491	pathogenic	-1.652	Destabilizing	0.996	D	0.697	prob.neutral	None	None	None	None	N
I/L	0.2738	likely_benign	0.3102	benign	-1.214	Destabilizing	0.011	N	0.265	neutral	N	0.486884537	None	None	N
I/M	0.2189	likely_benign	0.2605	benign	-1.085	Destabilizing	0.968	D	0.605	neutral	D	0.529734024	None	None	N
I/N	0.8222	likely_pathogenic	0.8777	pathogenic	-1.709	Destabilizing	0.995	D	0.702	prob.neutral	N	0.50857734	None	None	N
I/P	0.9641	likely_pathogenic	0.9724	pathogenic	-1.52	Destabilizing	0.996	D	0.702	prob.neutral	None	None	None	None	N
I/Q	0.9452	likely_pathogenic	0.9632	pathogenic	-1.908	Destabilizing	0.996	D	0.706	prob.neutral	None	None	None	None	N
I/R	0.8915	likely_pathogenic	0.9283	pathogenic	-1.02	Destabilizing	0.996	D	0.703	prob.neutral	None	None	None	None	N
I/S	0.8263	likely_pathogenic	0.8937	pathogenic	-2.311	Highly Destabilizing	0.968	D	0.659	neutral	N	0.507563382	None	None	N
I/T	0.6466	likely_pathogenic	0.7513	pathogenic	-2.144	Highly Destabilizing	0.896	D	0.631	neutral	N	0.510974905	None	None	N
I/V	0.1107	likely_benign	0.1309	benign	-1.52	Destabilizing	0.437	N	0.453	neutral	N	0.430236247	None	None	N
I/W	0.985	likely_pathogenic	0.9888	pathogenic	-1.795	Destabilizing	0.999	D	0.683	prob.neutral	None	None	None	None	N
I/Y	0.9208	likely_pathogenic	0.9403	pathogenic	-1.566	Destabilizing	0.996	D	0.676	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.