TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15065	45418;45419;45420	chr2:178621631;178621630;178621629	chr2:179486358;179486357;179486356
N2AB	13424	40495;40496;40497	chr2:178621631;178621630;178621629	chr2:179486358;179486357;179486356
N2A	12497	37714;37715;37716	chr2:178621631;178621630;178621629	chr2:179486358;179486357;179486356
N2B	6000	18223;18224;18225	chr2:178621631;178621630;178621629	chr2:179486358;179486357;179486356
Novex-1	6125	18598;18599;18600	chr2:178621631;178621630;178621629	chr2:179486358;179486357;179486356
Novex-2	6192	18799;18800;18801	chr2:178621631;178621630;178621629	chr2:179486358;179486357;179486356
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-102
• Domain position: 35
• Structural Position: 50
• Q(SASA): 0.1796
• 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
K/R	rs776374474	-0.692	0.884	D	0.312	0.515	0.395441342475	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	5.62E-05	None	0	None	0	0	0
K/R	rs776374474	-0.692	0.884	D	0.312	0.515	0.395441342475	gnomAD-4.0.0	1.59378E-06	None	None	None	None	N	None	0	0	None	0	2.78381E-05	None	0	0	0	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
K/A	0.8788	likely_pathogenic	0.8868	pathogenic	-1.093	Destabilizing	0.998	D	0.594	neutral	None	None	None	None	N
K/C	0.9046	likely_pathogenic	0.9411	pathogenic	-1.057	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
K/D	0.9705	likely_pathogenic	0.9742	pathogenic	-0.413	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
K/E	0.7184	likely_pathogenic	0.7063	pathogenic	-0.221	Destabilizing	0.996	D	0.511	neutral	D	0.82509512	None	None	N
K/F	0.9558	likely_pathogenic	0.9572	pathogenic	-0.671	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
K/G	0.941	likely_pathogenic	0.9524	pathogenic	-1.523	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
K/H	0.5793	likely_pathogenic	0.6392	pathogenic	-1.766	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
K/I	0.7971	likely_pathogenic	0.7832	pathogenic	0.067	Stabilizing	1.0	D	0.843	deleterious	D	0.757162329	None	None	N
K/L	0.7637	likely_pathogenic	0.7722	pathogenic	0.067	Stabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
K/M	0.6718	likely_pathogenic	0.6469	pathogenic	-0.066	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
K/N	0.9091	likely_pathogenic	0.9086	pathogenic	-0.91	Destabilizing	0.999	D	0.687	prob.neutral	D	0.713205174	None	None	N
K/P	0.9953	likely_pathogenic	0.9958	pathogenic	-0.292	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
K/Q	0.3871	ambiguous	0.3918	ambiguous	-0.832	Destabilizing	0.999	D	0.673	neutral	D	0.690885556	None	None	N
K/R	0.0894	likely_benign	0.106	benign	-0.736	Destabilizing	0.884	D	0.312	neutral	D	0.545647116	None	None	N
K/S	0.9108	likely_pathogenic	0.9142	pathogenic	-1.675	Destabilizing	0.998	D	0.547	neutral	None	None	None	None	N
K/T	0.7815	likely_pathogenic	0.7655	pathogenic	-1.233	Destabilizing	0.999	D	0.727	prob.delet.	D	0.734631692	None	None	N
K/V	0.7879	likely_pathogenic	0.7892	pathogenic	-0.292	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
K/W	0.9338	likely_pathogenic	0.9517	pathogenic	-0.518	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
K/Y	0.8913	likely_pathogenic	0.9128	pathogenic	-0.214	Destabilizing	1.0	D	0.818	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.