TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28652	86179;86180;86181	chr2:178560178;178560177;178560176	chr2:179424905;179424904;179424903
N2AB	27011	81256;81257;81258	chr2:178560178;178560177;178560176	chr2:179424905;179424904;179424903
N2A	26084	78475;78476;78477	chr2:178560178;178560177;178560176	chr2:179424905;179424904;179424903
N2B	19587	58984;58985;58986	chr2:178560178;178560177;178560176	chr2:179424905;179424904;179424903
Novex-1	19712	59359;59360;59361	chr2:178560178;178560177;178560176	chr2:179424905;179424904;179424903
Novex-2	19779	59560;59561;59562	chr2:178560178;178560177;178560176	chr2:179424905;179424904;179424903
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: Fn3-97
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.0893
• 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/L	None	None	1.0	D	0.816	0.455	0.814566475088	gnomAD-4.0.0	1.36844E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79896E-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
P/A	0.89	likely_pathogenic	0.8489	pathogenic	-2.076	Highly Destabilizing	0.999	D	0.799	deleterious	N	0.518411211	None	None	N
P/C	0.9913	likely_pathogenic	0.9865	pathogenic	-2.229	Highly Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
P/D	0.9997	likely_pathogenic	0.9996	pathogenic	-3.147	Highly Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
P/E	0.999	likely_pathogenic	0.9986	pathogenic	-3.03	Highly Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	N
P/F	0.9996	likely_pathogenic	0.9995	pathogenic	-1.373	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
P/G	0.9954	likely_pathogenic	0.993	pathogenic	-2.438	Highly Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
P/H	0.9982	likely_pathogenic	0.9975	pathogenic	-1.796	Destabilizing	1.0	D	0.758	deleterious	None	None	None	None	N
P/I	0.9937	likely_pathogenic	0.9921	pathogenic	-1.102	Destabilizing	1.0	D	0.76	deleterious	None	None	None	None	N
P/K	0.9993	likely_pathogenic	0.9991	pathogenic	-1.729	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
P/L	0.9687	likely_pathogenic	0.9587	pathogenic	-1.102	Destabilizing	1.0	D	0.816	deleterious	D	0.536008487	None	None	N
P/M	0.9975	likely_pathogenic	0.9966	pathogenic	-1.41	Destabilizing	1.0	D	0.756	deleterious	None	None	None	None	N
P/N	0.9993	likely_pathogenic	0.9991	pathogenic	-2.007	Highly Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
P/Q	0.9973	likely_pathogenic	0.9964	pathogenic	-2.083	Highly Destabilizing	1.0	D	0.811	deleterious	D	0.548885729	None	None	N
P/R	0.9971	likely_pathogenic	0.996	pathogenic	-1.319	Destabilizing	1.0	D	0.797	deleterious	D	0.537022445	None	None	N
P/S	0.9877	likely_pathogenic	0.9812	pathogenic	-2.477	Highly Destabilizing	1.0	D	0.733	deleterious	D	0.529678611	None	None	N
P/T	0.9878	likely_pathogenic	0.9829	pathogenic	-2.253	Highly Destabilizing	1.0	D	0.74	deleterious	D	0.54837875	None	None	N
P/V	0.9785	likely_pathogenic	0.9721	pathogenic	-1.403	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
P/W	0.9999	likely_pathogenic	0.9999	pathogenic	-1.655	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
P/Y	0.9996	likely_pathogenic	0.9995	pathogenic	-1.385	Destabilizing	1.0	D	0.83	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.