TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30446	91561;91562;91563	chr2:178551195;178551194;178551193	chr2:179415922;179415921;179415920
N2AB	28805	86638;86639;86640	chr2:178551195;178551194;178551193	chr2:179415922;179415921;179415920
N2A	27878	83857;83858;83859	chr2:178551195;178551194;178551193	chr2:179415922;179415921;179415920
N2B	21381	64366;64367;64368	chr2:178551195;178551194;178551193	chr2:179415922;179415921;179415920
Novex-1	21506	64741;64742;64743	chr2:178551195;178551194;178551193	chr2:179415922;179415921;179415920
Novex-2	21573	64942;64943;64944	chr2:178551195;178551194;178551193	chr2:179415922;179415921;179415920
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: Fn3-110
• Domain position: 25
• Structural Position: 27
• Q(SASA): 0.1522
• 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	rs1699285500	None	1.0	D	0.9	0.612	0.87861949169	gnomAD-4.0.0	1.09491E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.25939E-05	0	3.31367E-05

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	0.8852	likely_pathogenic	0.9009	pathogenic	-2.035	Highly Destabilizing	1.0	D	0.835	deleterious	D	0.576953734	None	None	N
P/C	0.9887	likely_pathogenic	0.9903	pathogenic	-1.341	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
P/D	0.9994	likely_pathogenic	0.9995	pathogenic	-2.539	Highly Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
P/E	0.9983	likely_pathogenic	0.9987	pathogenic	-2.438	Highly Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
P/F	0.9996	likely_pathogenic	0.9997	pathogenic	-1.363	Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
P/G	0.9933	likely_pathogenic	0.9942	pathogenic	-2.462	Highly Destabilizing	1.0	D	0.896	deleterious	None	None	None	None	N
P/H	0.9972	likely_pathogenic	0.9978	pathogenic	-2.218	Highly Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
P/I	0.9937	likely_pathogenic	0.9942	pathogenic	-0.892	Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	N
P/K	0.9989	likely_pathogenic	0.9991	pathogenic	-1.9	Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
P/L	0.979	likely_pathogenic	0.9821	pathogenic	-0.892	Destabilizing	1.0	D	0.9	deleterious	D	0.637841593	None	None	N
P/M	0.9972	likely_pathogenic	0.9977	pathogenic	-0.636	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
P/N	0.9989	likely_pathogenic	0.9991	pathogenic	-1.851	Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
P/Q	0.9967	likely_pathogenic	0.9975	pathogenic	-1.886	Destabilizing	1.0	D	0.833	deleterious	D	0.606579728	None	None	N
P/R	0.9954	likely_pathogenic	0.9965	pathogenic	-1.46	Destabilizing	1.0	D	0.894	deleterious	D	0.587572587	None	None	N
P/S	0.9811	likely_pathogenic	0.9843	pathogenic	-2.354	Highly Destabilizing	1.0	D	0.849	deleterious	D	0.546600885	None	None	N
P/T	0.9837	likely_pathogenic	0.9865	pathogenic	-2.145	Highly Destabilizing	1.0	D	0.845	deleterious	D	0.601068497	None	None	N
P/V	0.9785	likely_pathogenic	0.9801	pathogenic	-1.243	Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
P/W	0.9999	likely_pathogenic	0.9999	pathogenic	-1.804	Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	N
P/Y	0.9996	likely_pathogenic	0.9997	pathogenic	-1.5	Destabilizing	1.0	D	0.899	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.