TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6624	20095;20096;20097	chr2:178727708;178727707;178727706	chr2:179592435;179592434;179592433
N2AB	6307	19144;19145;19146	chr2:178727708;178727707;178727706	chr2:179592435;179592434;179592433
N2A	5380	16363;16364;16365	chr2:178727708;178727707;178727706	chr2:179592435;179592434;179592433
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: TTG
• RefSeq wild type template codon: AAC
• Domain: Ig-50
• Domain position: 51
• Structural Position: 127
• Q(SASA): 0.3378
• 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/F	rs78279193	-0.934	0.723	N	0.609	0.196	0.337868961071	gnomAD-4.0.0	3.18506E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.8843E-05	0	0	0	3.02682E-05

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	0.2131	likely_benign	0.1824	benign	-1.005	Destabilizing	0.339	N	0.537	neutral	None	None	None	None	N
L/C	0.4995	ambiguous	0.4522	ambiguous	-0.767	Destabilizing	0.995	D	0.602	neutral	None	None	None	None	N
L/D	0.6612	likely_pathogenic	0.5903	pathogenic	0.357	Stabilizing	0.554	D	0.673	neutral	None	None	None	None	N
L/E	0.3093	likely_benign	0.2687	benign	0.355	Stabilizing	0.024	N	0.525	neutral	None	None	None	None	N
L/F	0.1155	likely_benign	0.105	benign	-0.603	Destabilizing	0.723	D	0.609	neutral	N	0.496631015	None	None	N
L/G	0.5002	ambiguous	0.4434	ambiguous	-1.287	Destabilizing	0.834	D	0.675	neutral	None	None	None	None	N
L/H	0.2003	likely_benign	0.1861	benign	-0.561	Destabilizing	0.965	D	0.659	neutral	None	None	None	None	N
L/I	0.079	likely_benign	0.0702	benign	-0.335	Destabilizing	None	N	0.283	neutral	None	None	None	None	N
L/K	0.2104	likely_benign	0.1882	benign	-0.411	Destabilizing	0.001	N	0.508	neutral	None	None	None	None	N
L/M	0.0855	likely_benign	0.0796	benign	-0.41	Destabilizing	0.007	N	0.271	neutral	N	0.488668524	None	None	N
L/N	0.3461	ambiguous	0.2937	benign	-0.242	Destabilizing	0.946	D	0.673	neutral	None	None	None	None	N
L/P	0.5706	likely_pathogenic	0.5403	ambiguous	-0.525	Destabilizing	0.982	D	0.677	prob.neutral	None	None	None	None	N
L/Q	0.1227	likely_benign	0.1203	benign	-0.333	Destabilizing	0.085	N	0.477	neutral	None	None	None	None	N
L/R	0.1708	likely_benign	0.1618	benign	-0.064	Destabilizing	0.331	N	0.675	neutral	None	None	None	None	N
L/S	0.2213	likely_benign	0.1868	benign	-0.955	Destabilizing	0.652	D	0.629	neutral	N	0.481222558	None	None	N
L/T	0.1544	likely_benign	0.1348	benign	-0.833	Destabilizing	0.427	N	0.55	neutral	None	None	None	None	N
L/V	0.0838	likely_benign	0.0777	benign	-0.525	Destabilizing	0.015	N	0.507	neutral	N	0.499328186	None	None	N
L/W	0.2168	likely_benign	0.2012	benign	-0.642	Destabilizing	0.996	D	0.659	neutral	N	0.51821799	None	None	N
L/Y	0.3422	ambiguous	0.3039	benign	-0.377	Destabilizing	0.452	N	0.64	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.