TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8741	26446;26447;26448	chr2:178714553;178714552;178714551	chr2:179579280;179579279;179579278
N2AB	8424	25495;25496;25497	chr2:178714553;178714552;178714551	chr2:179579280;179579279;179579278
N2A	7497	22714;22715;22716	chr2:178714553;178714552;178714551	chr2:179579280;179579279;179579278
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: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-73
• Domain position: 6
• Structural Position: 7
• Q(SASA): 0.5372
• Predicted PPI site: I

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
K/E	rs538959125	0.578	0.114	D	0.547	0.279	0.3691244813	gnomAD-2.1.1	1.78299E-04	None	None	None	None	I	None	0	0	None	0	2.53676E-03	None	0	None	0	0	0
K/E	rs538959125	0.578	0.114	D	0.547	0.279	0.3691244813	gnomAD-3.1.2	9.2E-05	None	None	None	None	I	None	0	6.55E-05	0	0	2.50675E-03	None	0	0	0	0	0
K/E	rs538959125	0.578	0.114	D	0.547	0.279	0.3691244813	1000 genomes	3.99361E-04	None	None	None	None	I	None	0	0	None	None	2E-03	0	None	None	None	0	None
K/E	rs538959125	0.578	0.114	D	0.547	0.279	0.3691244813	gnomAD-4.0.0	3.2426E-05	None	None	None	None	I	None	0	1.68294E-05	None	0	1.03042E-03	None	0	0	0	0	8.06218E-05
K/Q	None	None	0.269	N	0.568	0.344	0.248417906384	gnomAD-4.0.0	6.89001E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.17583E-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
K/A	0.455	ambiguous	0.6163	pathogenic	-0.348	Destabilizing	0.221	N	0.552	neutral	None	None	None	None	I
K/C	0.8249	likely_pathogenic	0.8855	pathogenic	-0.487	Destabilizing	0.938	D	0.691	prob.neutral	None	None	None	None	I
K/D	0.6255	likely_pathogenic	0.7548	pathogenic	0.433	Stabilizing	0.665	D	0.583	neutral	None	None	None	None	I
K/E	0.2785	likely_benign	0.4112	ambiguous	0.513	Stabilizing	0.114	N	0.547	neutral	D	0.523919986	None	None	I
K/F	0.7729	likely_pathogenic	0.8797	pathogenic	-0.254	Destabilizing	0.616	D	0.683	prob.neutral	None	None	None	None	I
K/G	0.5163	ambiguous	0.6658	pathogenic	-0.633	Destabilizing	0.361	N	0.555	neutral	None	None	None	None	I
K/H	0.3509	ambiguous	0.4387	ambiguous	-0.769	Destabilizing	0.95	D	0.623	neutral	None	None	None	None	I
K/I	0.4344	ambiguous	0.6108	pathogenic	0.355	Stabilizing	0.028	N	0.691	prob.neutral	None	None	None	None	I
K/L	0.4201	ambiguous	0.5692	pathogenic	0.355	Stabilizing	0.008	N	0.555	neutral	None	None	None	None	I
K/M	0.2667	likely_benign	0.3789	ambiguous	0.026	Stabilizing	0.578	D	0.616	neutral	N	0.521918201	None	None	I
K/N	0.4307	ambiguous	0.5724	pathogenic	-0.033	Destabilizing	0.6	D	0.551	neutral	N	0.498280537	None	None	I
K/P	0.4643	ambiguous	0.5718	pathogenic	0.15	Stabilizing	0.801	D	0.641	neutral	None	None	None	None	I
K/Q	0.169	likely_benign	0.2264	benign	-0.088	Destabilizing	0.269	N	0.568	neutral	N	0.49224015	None	None	I
K/R	0.1007	likely_benign	0.1153	benign	-0.122	Destabilizing	0.002	N	0.307	neutral	N	0.493899218	None	None	I
K/S	0.4949	ambiguous	0.6459	pathogenic	-0.694	Destabilizing	0.221	N	0.545	neutral	None	None	None	None	I
K/T	0.2517	likely_benign	0.3885	ambiguous	-0.42	Destabilizing	0.001	N	0.327	neutral	N	0.500482583	None	None	I
K/V	0.4317	ambiguous	0.5916	pathogenic	0.15	Stabilizing	0.037	N	0.529	neutral	None	None	None	None	I
K/W	0.7882	likely_pathogenic	0.8742	pathogenic	-0.172	Destabilizing	0.986	D	0.697	prob.neutral	None	None	None	None	I
K/Y	0.5906	likely_pathogenic	0.7199	pathogenic	0.14	Stabilizing	0.158	N	0.673	neutral	None	None	None	None	I

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.