TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19370	58333;58334;58335	chr2:178594386;178594385;178594384	chr2:179459113;179459112;179459111
N2AB	17729	53410;53411;53412	chr2:178594386;178594385;178594384	chr2:179459113;179459112;179459111
N2A	16802	50629;50630;50631	chr2:178594386;178594385;178594384	chr2:179459113;179459112;179459111
N2B	10305	31138;31139;31140	chr2:178594386;178594385;178594384	chr2:179459113;179459112;179459111
Novex-1	10430	31513;31514;31515	chr2:178594386;178594385;178594384	chr2:179459113;179459112;179459111
Novex-2	10497	31714;31715;31716	chr2:178594386;178594385;178594384	chr2:179459113;179459112;179459111
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-28
• Domain position: 87
• Structural Position: 120
• Q(SASA): 0.3952
• 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
P/A	None	None	1.0	N	0.787	0.424	0.362758974969	gnomAD-4.0.0	1.37864E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.8084E-06	0	0
P/T	rs890232785	None	1.0	N	0.829	0.445	None	gnomAD-4.0.0	6.8932E-07	None	None	None	None	N	None	3.02645E-05	0	None	0	0	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
P/A	0.4129	ambiguous	0.3511	ambiguous	-1.495	Destabilizing	1.0	D	0.787	deleterious	N	0.481026342	None	None	N
P/C	0.9583	likely_pathogenic	0.9468	pathogenic	-1.093	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
P/D	0.9847	likely_pathogenic	0.9805	pathogenic	-1.528	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
P/E	0.9624	likely_pathogenic	0.9488	pathogenic	-1.572	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
P/F	0.9599	likely_pathogenic	0.9409	pathogenic	-1.33	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
P/G	0.9171	likely_pathogenic	0.9043	pathogenic	-1.748	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
P/H	0.8433	likely_pathogenic	0.7845	pathogenic	-1.13	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
P/I	0.9509	likely_pathogenic	0.9276	pathogenic	-0.912	Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
P/K	0.969	likely_pathogenic	0.9602	pathogenic	-1.086	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
P/L	0.8503	likely_pathogenic	0.794	pathogenic	-0.912	Destabilizing	1.0	D	0.864	deleterious	N	0.501359096	None	None	N
P/M	0.9403	likely_pathogenic	0.9228	pathogenic	-0.69	Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
P/N	0.9642	likely_pathogenic	0.9469	pathogenic	-0.872	Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
P/Q	0.8845	likely_pathogenic	0.8499	pathogenic	-1.171	Destabilizing	1.0	D	0.849	deleterious	D	0.523048203	None	None	N
P/R	0.9267	likely_pathogenic	0.9007	pathogenic	-0.473	Destabilizing	1.0	D	0.883	deleterious	N	0.513982849	None	None	N
P/S	0.7901	likely_pathogenic	0.7299	pathogenic	-1.351	Destabilizing	1.0	D	0.824	deleterious	N	0.49528271	None	None	N
P/T	0.8225	likely_pathogenic	0.7645	pathogenic	-1.299	Destabilizing	1.0	D	0.829	deleterious	N	0.518021774	None	None	N
P/V	0.875	likely_pathogenic	0.8294	pathogenic	-1.073	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
P/W	0.9802	likely_pathogenic	0.9723	pathogenic	-1.394	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
P/Y	0.9386	likely_pathogenic	0.9107	pathogenic	-1.133	Destabilizing	1.0	D	0.891	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.