TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14767	44524;44525;44526	chr2:178629426;178629425;178629424	chr2:179494153;179494152;179494151
N2AB	13126	39601;39602;39603	chr2:178629426;178629425;178629424	chr2:179494153;179494152;179494151
N2A	12199	36820;36821;36822	chr2:178629426;178629425;178629424	chr2:179494153;179494152;179494151
N2B	5702	17329;17330;17331	chr2:178629426;178629425;178629424	chr2:179494153;179494152;179494151
Novex-1	5827	17704;17705;17706	chr2:178629426;178629425;178629424	chr2:179494153;179494152;179494151
Novex-2	5894	17905;17906;17907	chr2:178629426;178629425;178629424	chr2:179494153;179494152;179494151
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-99
• Domain position: 3
• Structural Position: 4
• Q(SASA): 0.1257
• 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
L/V	None	None	0.4	N	0.408	0.057	0.253205268125	gnomAD-4.0.0	1.59332E-06	None	None	None	None	N	None	5.67472E-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
L/A	0.4	ambiguous	0.4726	ambiguous	-1.139	Destabilizing	0.985	D	0.596	neutral	None	None	None	None	N
L/C	0.6816	likely_pathogenic	0.7303	pathogenic	-0.759	Destabilizing	1.0	D	0.595	neutral	None	None	None	None	N
L/D	0.8344	likely_pathogenic	0.8751	pathogenic	-0.322	Destabilizing	0.991	D	0.625	neutral	None	None	None	None	N
L/E	0.448	ambiguous	0.5167	ambiguous	-0.363	Destabilizing	0.671	D	0.515	neutral	None	None	None	None	N
L/F	0.2847	likely_benign	0.3323	benign	-0.781	Destabilizing	0.996	D	0.666	neutral	None	None	None	None	N
L/G	0.7165	likely_pathogenic	0.7569	pathogenic	-1.387	Destabilizing	0.998	D	0.624	neutral	None	None	None	None	N
L/H	0.379	ambiguous	0.4239	ambiguous	-0.473	Destabilizing	1.0	D	0.652	neutral	None	None	None	None	N
L/I	0.1064	likely_benign	0.113	benign	-0.57	Destabilizing	0.971	D	0.615	neutral	None	None	None	None	N
L/K	0.3599	ambiguous	0.372	ambiguous	-0.669	Destabilizing	0.996	D	0.6	neutral	None	None	None	None	N
L/M	0.1693	likely_benign	0.1916	benign	-0.511	Destabilizing	0.911	D	0.529	neutral	N	0.439552293	None	None	N
L/N	0.5554	ambiguous	0.5838	pathogenic	-0.498	Destabilizing	0.998	D	0.661	neutral	None	None	None	None	N
L/P	0.8117	likely_pathogenic	0.8513	pathogenic	-0.726	Destabilizing	0.999	D	0.663	neutral	N	0.495529796	None	None	N
L/Q	0.1956	likely_benign	0.2273	benign	-0.7	Destabilizing	0.994	D	0.64	neutral	N	0.51951684	None	None	N
L/R	0.2748	likely_benign	0.2893	benign	-0.061	Destabilizing	0.994	D	0.635	neutral	N	0.453199503	None	None	N
L/S	0.4506	ambiguous	0.5084	ambiguous	-1.084	Destabilizing	0.971	D	0.601	neutral	None	None	None	None	N
L/T	0.3237	likely_benign	0.3578	ambiguous	-1.014	Destabilizing	0.671	D	0.411	neutral	None	None	None	None	N
L/V	0.1153	likely_benign	0.1259	benign	-0.726	Destabilizing	0.4	N	0.408	neutral	N	0.440193694	None	None	N
L/W	0.4497	ambiguous	0.5134	ambiguous	-0.779	Destabilizing	1.0	D	0.657	neutral	None	None	None	None	N
L/Y	0.564	likely_pathogenic	0.6072	pathogenic	-0.566	Destabilizing	0.999	D	0.614	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.