TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24886	74881;74882;74883	chr2:178571476;178571475;178571474	chr2:179436203;179436202;179436201
N2AB	23245	69958;69959;69960	chr2:178571476;178571475;178571474	chr2:179436203;179436202;179436201
N2A	22318	67177;67178;67179	chr2:178571476;178571475;178571474	chr2:179436203;179436202;179436201
N2B	15821	47686;47687;47688	chr2:178571476;178571475;178571474	chr2:179436203;179436202;179436201
Novex-1	15946	48061;48062;48063	chr2:178571476;178571475;178571474	chr2:179436203;179436202;179436201
Novex-2	16013	48262;48263;48264	chr2:178571476;178571475;178571474	chr2:179436203;179436202;179436201
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-68
• Domain position: 79
• Structural Position: 111
• Q(SASA): 0.1539
• 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
E/K	rs1239424185	-0.507	0.999	N	0.462	0.38	0.326616659874	gnomAD-4.0.0	1.36875E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.7992E-06	0	0
E/Q	None	None	1.0	N	0.573	0.252	0.278143212241	gnomAD-4.0.0	1.36875E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.7992E-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
E/A	0.7126	likely_pathogenic	0.6542	pathogenic	-0.552	Destabilizing	0.999	D	0.61	neutral	N	0.475595066	None	None	N
E/C	0.9776	likely_pathogenic	0.9722	pathogenic	-0.559	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
E/D	0.9467	likely_pathogenic	0.9399	pathogenic	-1.457	Destabilizing	0.999	D	0.421	neutral	N	0.512514819	None	None	N
E/F	0.9901	likely_pathogenic	0.9857	pathogenic	-0.979	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
E/G	0.858	likely_pathogenic	0.8307	pathogenic	-0.864	Destabilizing	1.0	D	0.725	prob.delet.	D	0.530619074	None	None	N
E/H	0.9771	likely_pathogenic	0.968	pathogenic	-1.228	Destabilizing	1.0	D	0.633	neutral	None	None	None	None	N
E/I	0.8804	likely_pathogenic	0.8387	pathogenic	0.28	Stabilizing	1.0	D	0.872	deleterious	None	None	None	None	N
E/K	0.7838	likely_pathogenic	0.7394	pathogenic	-0.789	Destabilizing	0.999	D	0.462	neutral	N	0.475456935	None	None	N
E/L	0.9548	likely_pathogenic	0.9379	pathogenic	0.28	Stabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
E/M	0.8926	likely_pathogenic	0.8567	pathogenic	0.717	Stabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
E/N	0.9615	likely_pathogenic	0.9522	pathogenic	-1.021	Destabilizing	1.0	D	0.657	neutral	None	None	None	None	N
E/P	0.9994	likely_pathogenic	0.9993	pathogenic	0.024	Stabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
E/Q	0.4158	ambiguous	0.3548	ambiguous	-0.868	Destabilizing	1.0	D	0.573	neutral	N	0.468113101	None	None	N
E/R	0.8768	likely_pathogenic	0.8448	pathogenic	-0.852	Destabilizing	1.0	D	0.657	neutral	None	None	None	None	N
E/S	0.8259	likely_pathogenic	0.7859	pathogenic	-1.427	Destabilizing	0.999	D	0.525	neutral	None	None	None	None	N
E/T	0.8358	likely_pathogenic	0.7853	pathogenic	-1.146	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
E/V	0.709	likely_pathogenic	0.6288	pathogenic	0.024	Stabilizing	1.0	D	0.786	deleterious	N	0.469852562	None	None	N
E/W	0.9973	likely_pathogenic	0.9964	pathogenic	-1.238	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
E/Y	0.9882	likely_pathogenic	0.9836	pathogenic	-0.831	Destabilizing	1.0	D	0.836	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.