TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6332	19219;19220;19221	chr2:178729044;178729043;178729042	chr2:179593771;179593770;179593769
N2AB	6015	18268;18269;18270	chr2:178729044;178729043;178729042	chr2:179593771;179593770;179593769
N2A	5088	15487;15488;15489	chr2:178729044;178729043;178729042	chr2:179593771;179593770;179593769
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: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-47
• Domain position: 41
• Structural Position: 58
• Q(SASA): 0.2124
• 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	rs1441559155	-1.337	0.001	N	0.349	0.111	0.474010150167	gnomAD-2.1.1	4.06E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.28E-05	None	0	0	0
L/V	rs1441559155	-1.337	0.001	N	0.349	0.111	0.474010150167	gnomAD-4.0.0	1.59358E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43464E-05	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	0.3732	ambiguous	0.3451	ambiguous	-2.11	Highly Destabilizing	0.241	N	0.481	neutral	None	None	None	None	N
L/C	0.6518	likely_pathogenic	0.6356	pathogenic	-1.474	Destabilizing	0.981	D	0.566	neutral	None	None	None	None	N
L/D	0.9214	likely_pathogenic	0.9033	pathogenic	-1.632	Destabilizing	0.818	D	0.693	prob.neutral	None	None	None	None	N
L/E	0.701	likely_pathogenic	0.6377	pathogenic	-1.485	Destabilizing	0.69	D	0.663	neutral	None	None	None	None	N
L/F	0.2066	likely_benign	0.203	benign	-1.246	Destabilizing	0.003	N	0.361	neutral	N	0.508353985	None	None	N
L/G	0.8028	likely_pathogenic	0.7664	pathogenic	-2.566	Highly Destabilizing	0.818	D	0.644	neutral	None	None	None	None	N
L/H	0.5197	ambiguous	0.4695	ambiguous	-1.663	Destabilizing	0.008	N	0.52	neutral	D	0.535865989	None	None	N
L/I	0.0637	likely_benign	0.0634	benign	-0.848	Destabilizing	0.001	N	0.231	neutral	N	0.427857663	None	None	N
L/K	0.5908	likely_pathogenic	0.5228	ambiguous	-1.584	Destabilizing	0.818	D	0.616	neutral	None	None	None	None	N
L/M	0.1389	likely_benign	0.135	benign	-0.801	Destabilizing	0.69	D	0.497	neutral	None	None	None	None	N
L/N	0.7482	likely_pathogenic	0.7122	pathogenic	-1.713	Destabilizing	0.69	D	0.7	prob.neutral	None	None	None	None	N
L/P	0.7098	likely_pathogenic	0.6638	pathogenic	-1.243	Destabilizing	0.912	D	0.701	prob.neutral	D	0.52409161	None	None	N
L/Q	0.4457	ambiguous	0.3749	ambiguous	-1.665	Destabilizing	0.818	D	0.661	neutral	None	None	None	None	N
L/R	0.4681	ambiguous	0.4008	ambiguous	-1.193	Destabilizing	0.627	D	0.653	neutral	D	0.52886455	None	None	N
L/S	0.5818	likely_pathogenic	0.5297	ambiguous	-2.436	Highly Destabilizing	0.69	D	0.583	neutral	None	None	None	None	N
L/T	0.3131	likely_benign	0.2948	benign	-2.137	Highly Destabilizing	0.388	N	0.5	neutral	None	None	None	None	N
L/V	0.0829	likely_benign	0.0805	benign	-1.243	Destabilizing	0.001	N	0.349	neutral	N	0.446483496	None	None	N
L/W	0.4341	ambiguous	0.4065	ambiguous	-1.4	Destabilizing	0.981	D	0.671	neutral	None	None	None	None	N
L/Y	0.5895	likely_pathogenic	0.5661	pathogenic	-1.158	Destabilizing	0.527	D	0.537	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.