TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18131	54616;54617;54618	chr2:178604296;178604295;178604294	chr2:179469023;179469022;179469021
N2AB	16490	49693;49694;49695	chr2:178604296;178604295;178604294	chr2:179469023;179469022;179469021
N2A	15563	46912;46913;46914	chr2:178604296;178604295;178604294	chr2:179469023;179469022;179469021
N2B	9066	27421;27422;27423	chr2:178604296;178604295;178604294	chr2:179469023;179469022;179469021
Novex-1	9191	27796;27797;27798	chr2:178604296;178604295;178604294	chr2:179469023;179469022;179469021
Novex-2	9258	27997;27998;27999	chr2:178604296;178604295;178604294	chr2:179469023;179469022;179469021
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: Fn3-19
• Domain position: 67
• Structural Position: 97
• Q(SASA): 0.1112
• 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/H	None	None	1.0	D	0.815	0.817	0.952985272838	gnomAD-4.0.0	2.11844E-06	None	None	None	None	N	None	0	0	None	0	3.01896E-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
L/A	0.9672	likely_pathogenic	0.9734	pathogenic	-2.465	Highly Destabilizing	0.999	D	0.831	deleterious	None	None	None	None	N
L/C	0.9448	likely_pathogenic	0.9598	pathogenic	-1.731	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
L/D	0.9986	likely_pathogenic	0.9989	pathogenic	-2.551	Highly Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
L/E	0.9943	likely_pathogenic	0.9966	pathogenic	-2.331	Highly Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
L/F	0.8523	likely_pathogenic	0.8765	pathogenic	-1.495	Destabilizing	1.0	D	0.875	deleterious	D	0.646170905	None	None	N
L/G	0.9869	likely_pathogenic	0.9892	pathogenic	-3.009	Highly Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
L/H	0.987	likely_pathogenic	0.9913	pathogenic	-2.379	Highly Destabilizing	1.0	D	0.815	deleterious	D	0.646978122	None	None	N
L/I	0.457	ambiguous	0.497	ambiguous	-0.905	Destabilizing	0.999	D	0.835	deleterious	D	0.619623772	None	None	N
L/K	0.9892	likely_pathogenic	0.9911	pathogenic	-1.901	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
L/M	0.4373	ambiguous	0.4942	ambiguous	-0.819	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
L/N	0.9869	likely_pathogenic	0.9914	pathogenic	-2.218	Highly Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	N
L/P	0.9914	likely_pathogenic	0.993	pathogenic	-1.404	Destabilizing	1.0	D	0.859	deleterious	D	0.646978122	None	None	N
L/Q	0.9807	likely_pathogenic	0.987	pathogenic	-2.093	Highly Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
L/R	0.9817	likely_pathogenic	0.9863	pathogenic	-1.577	Destabilizing	1.0	D	0.857	deleterious	D	0.630726596	None	None	N
L/S	0.9951	likely_pathogenic	0.9965	pathogenic	-2.949	Highly Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
L/T	0.9686	likely_pathogenic	0.9762	pathogenic	-2.578	Highly Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
L/V	0.532	ambiguous	0.6082	pathogenic	-1.404	Destabilizing	0.999	D	0.845	deleterious	D	0.581427327	None	None	N
L/W	0.981	likely_pathogenic	0.9855	pathogenic	-1.846	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
L/Y	0.9789	likely_pathogenic	0.985	pathogenic	-1.547	Destabilizing	1.0	D	0.833	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.