TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6472	19639;19640;19641	chr2:178728512;178728511;178728510	chr2:179593239;179593238;179593237
N2AB	6155	18688;18689;18690	chr2:178728512;178728511;178728510	chr2:179593239;179593238;179593237
N2A	5228	15907;15908;15909	chr2:178728512;178728511;178728510	chr2:179593239;179593238;179593237
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTA
• RefSeq wild type template codon: AAT
• Domain: Ig-48
• Domain position: 88
• Structural Position: 174
• Q(SASA): 0.1401
• 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	None	None	0.992	D	0.639	0.295	0.471941563831	gnomAD-4.0.0	1.60041E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.87783E-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	0.8967	likely_pathogenic	0.8855	pathogenic	-2.721	Highly Destabilizing	0.997	D	0.692	prob.neutral	None	None	None	None	N
L/C	0.8484	likely_pathogenic	0.8511	pathogenic	-2.19	Highly Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
L/D	0.9989	likely_pathogenic	0.9986	pathogenic	-2.999	Highly Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
L/E	0.9914	likely_pathogenic	0.9888	pathogenic	-2.739	Highly Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
L/F	0.3415	ambiguous	0.3137	benign	-1.637	Destabilizing	0.999	D	0.835	deleterious	N	0.510755116	None	None	N
L/G	0.9814	likely_pathogenic	0.9796	pathogenic	-3.314	Highly Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
L/H	0.9665	likely_pathogenic	0.9591	pathogenic	-2.757	Highly Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
L/I	0.1025	likely_benign	0.1023	benign	-0.987	Destabilizing	0.992	D	0.639	neutral	D	0.525047776	None	None	N
L/K	0.9853	likely_pathogenic	0.9831	pathogenic	-2.094	Highly Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
L/M	0.285	likely_benign	0.273	benign	-1.064	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
L/N	0.9922	likely_pathogenic	0.9908	pathogenic	-2.537	Highly Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	N
L/P	0.9884	likely_pathogenic	0.9856	pathogenic	-1.548	Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	N
L/Q	0.9527	likely_pathogenic	0.9451	pathogenic	-2.341	Highly Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
L/R	0.9633	likely_pathogenic	0.9592	pathogenic	-1.87	Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
L/S	0.9786	likely_pathogenic	0.9724	pathogenic	-3.29	Highly Destabilizing	0.999	D	0.883	deleterious	D	0.546256064	None	None	N
L/T	0.9324	likely_pathogenic	0.9152	pathogenic	-2.866	Highly Destabilizing	0.999	D	0.823	deleterious	None	None	None	None	N
L/V	0.1201	likely_benign	0.1147	benign	-1.548	Destabilizing	0.767	D	0.383	neutral	N	0.477136398	None	None	N
L/W	0.8777	likely_pathogenic	0.8608	pathogenic	-2.008	Highly Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
L/Y	0.9161	likely_pathogenic	0.9094	pathogenic	-1.742	Destabilizing	1.0	D	0.847	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.