TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26747	80464;80465;80466	chr2:178565893;178565892;178565891	chr2:179430620;179430619;179430618
N2AB	25106	75541;75542;75543	chr2:178565893;178565892;178565891	chr2:179430620;179430619;179430618
N2A	24179	72760;72761;72762	chr2:178565893;178565892;178565891	chr2:179430620;179430619;179430618
N2B	17682	53269;53270;53271	chr2:178565893;178565892;178565891	chr2:179430620;179430619;179430618
Novex-1	17807	53644;53645;53646	chr2:178565893;178565892;178565891	chr2:179430620;179430619;179430618
Novex-2	17874	53845;53846;53847	chr2:178565893;178565892;178565891	chr2:179430620;179430619;179430618
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Fn3-82
• Domain position: 65
• Structural Position: 97
• Q(SASA): 0.1289
• 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/I	rs779100100	-1.44	0.995	D	0.835	0.724	0.867892837264	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
L/I	rs779100100	-1.44	0.995	D	0.835	0.724	0.867892837264	gnomAD-4.0.0	3.18327E-06	None	None	None	None	N	None	0	0	None	0	2.77423E-05	None	0	0	2.85919E-06	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	0.9772	likely_pathogenic	0.9747	pathogenic	-2.62	Highly Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
L/C	0.9478	likely_pathogenic	0.9371	pathogenic	-2.276	Highly Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
L/D	0.9995	likely_pathogenic	0.9995	pathogenic	-2.912	Highly Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
L/E	0.9975	likely_pathogenic	0.9973	pathogenic	-2.782	Highly Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
L/F	0.8148	likely_pathogenic	0.8257	pathogenic	-1.879	Destabilizing	1.0	D	0.867	deleterious	D	0.656153985	None	None	N
L/G	0.9952	likely_pathogenic	0.9948	pathogenic	-3.09	Highly Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
L/H	0.9936	likely_pathogenic	0.9934	pathogenic	-2.378	Highly Destabilizing	1.0	D	0.813	deleterious	D	0.672980563	None	None	N
L/I	0.3227	likely_benign	0.3347	benign	-1.298	Destabilizing	0.995	D	0.835	deleterious	D	0.645858377	None	None	N
L/K	0.9946	likely_pathogenic	0.9947	pathogenic	-2.011	Highly Destabilizing	0.999	D	0.846	deleterious	None	None	None	None	N
L/M	0.3677	ambiguous	0.3854	ambiguous	-1.228	Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
L/N	0.9953	likely_pathogenic	0.995	pathogenic	-2.199	Highly Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
L/P	0.9966	likely_pathogenic	0.997	pathogenic	-1.716	Destabilizing	1.0	D	0.857	deleterious	D	0.672980563	None	None	N
L/Q	0.9865	likely_pathogenic	0.9864	pathogenic	-2.249	Highly Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
L/R	0.9891	likely_pathogenic	0.9885	pathogenic	-1.48	Destabilizing	1.0	D	0.851	deleterious	D	0.672980563	None	None	N
L/S	0.9959	likely_pathogenic	0.9955	pathogenic	-2.902	Highly Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
L/T	0.9735	likely_pathogenic	0.9717	pathogenic	-2.631	Highly Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
L/V	0.4357	ambiguous	0.422	ambiguous	-1.716	Destabilizing	0.996	D	0.843	deleterious	D	0.599304006	None	None	N
L/W	0.9846	likely_pathogenic	0.985	pathogenic	-2.126	Highly Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
L/Y	0.9884	likely_pathogenic	0.9891	pathogenic	-1.89	Destabilizing	0.999	D	0.827	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.