TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15493	46702;46703;46704	chr2:178619840;178619839;178619838	chr2:179484567;179484566;179484565
N2AB	13852	41779;41780;41781	chr2:178619840;178619839;178619838	chr2:179484567;179484566;179484565
N2A	12925	38998;38999;39000	chr2:178619840;178619839;178619838	chr2:179484567;179484566;179484565
N2B	6428	19507;19508;19509	chr2:178619840;178619839;178619838	chr2:179484567;179484566;179484565
Novex-1	6553	19882;19883;19884	chr2:178619840;178619839;178619838	chr2:179484567;179484566;179484565
Novex-2	6620	20083;20084;20085	chr2:178619840;178619839;178619838	chr2:179484567;179484566;179484565
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Ig-107
• Domain position: 14
• Structural Position: 23
• Q(SASA): 0.4746
• 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/S	rs1173523537	-0.982	1.0	N	0.76	0.389	0.393775345888	gnomAD-4.0.0	1.59509E-06	None	None	None	None	N	None	0	2.29263E-05	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	0.1848	likely_benign	0.1562	benign	-1.028	Destabilizing	1.0	D	0.693	prob.neutral	N	0.470006298	None	None	N
P/C	0.8755	likely_pathogenic	0.8557	pathogenic	-0.714	Destabilizing	1.0	D	0.76	deleterious	None	None	None	None	N
P/D	0.9009	likely_pathogenic	0.8801	pathogenic	-0.722	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
P/E	0.6404	likely_pathogenic	0.5722	pathogenic	-0.782	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
P/F	0.8909	likely_pathogenic	0.8664	pathogenic	-0.939	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
P/G	0.7361	likely_pathogenic	0.7173	pathogenic	-1.266	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
P/H	0.6566	likely_pathogenic	0.6183	pathogenic	-0.795	Destabilizing	1.0	D	0.745	deleterious	N	0.510643067	None	None	N
P/I	0.574	likely_pathogenic	0.5201	ambiguous	-0.51	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
P/K	0.7131	likely_pathogenic	0.6832	pathogenic	-0.891	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
P/L	0.352	ambiguous	0.3087	benign	-0.51	Destabilizing	1.0	D	0.785	deleterious	N	0.49229957	None	None	N
P/M	0.6775	likely_pathogenic	0.6231	pathogenic	-0.403	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
P/N	0.8271	likely_pathogenic	0.8055	pathogenic	-0.601	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
P/Q	0.4881	ambiguous	0.4489	ambiguous	-0.816	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
P/R	0.5473	ambiguous	0.5165	ambiguous	-0.338	Destabilizing	1.0	D	0.793	deleterious	N	0.484543749	None	None	N
P/S	0.415	ambiguous	0.3768	ambiguous	-1.049	Destabilizing	1.0	D	0.76	deleterious	N	0.503505563	None	None	N
P/T	0.3144	likely_benign	0.2787	benign	-1.003	Destabilizing	1.0	D	0.753	deleterious	N	0.464857289	None	None	N
P/V	0.399	ambiguous	0.3579	ambiguous	-0.646	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
P/W	0.9462	likely_pathogenic	0.9327	pathogenic	-1.066	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
P/Y	0.8648	likely_pathogenic	0.8476	pathogenic	-0.78	Destabilizing	1.0	D	0.762	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.