TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23995	72208;72209;72210	chr2:178574149;178574148;178574147	chr2:179438876;179438875;179438874
N2AB	22354	67285;67286;67287	chr2:178574149;178574148;178574147	chr2:179438876;179438875;179438874
N2A	21427	64504;64505;64506	chr2:178574149;178574148;178574147	chr2:179438876;179438875;179438874
N2B	14930	45013;45014;45015	chr2:178574149;178574148;178574147	chr2:179438876;179438875;179438874
Novex-1	15055	45388;45389;45390	chr2:178574149;178574148;178574147	chr2:179438876;179438875;179438874
Novex-2	15122	45589;45590;45591	chr2:178574149;178574148;178574147	chr2:179438876;179438875;179438874
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-62
• Domain position: 72
• Structural Position: 104
• Q(SASA): 0.1091
• 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
Y/H	None	None	1.0	D	0.831	0.848	0.841363702225	gnomAD-4.0.0	1.59169E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85909E-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
Y/A	0.9817	likely_pathogenic	0.9815	pathogenic	-2.974	Highly Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
Y/C	0.7083	likely_pathogenic	0.7163	pathogenic	-1.798	Destabilizing	1.0	D	0.833	deleterious	D	0.667131778	None	None	N
Y/D	0.991	likely_pathogenic	0.9917	pathogenic	-3.169	Highly Destabilizing	1.0	D	0.833	deleterious	D	0.69266989	None	None	N
Y/E	0.9963	likely_pathogenic	0.9962	pathogenic	-2.955	Highly Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
Y/F	0.2196	likely_benign	0.2157	benign	-0.994	Destabilizing	0.999	D	0.764	deleterious	D	0.631419501	None	None	N
Y/G	0.9693	likely_pathogenic	0.9701	pathogenic	-3.409	Highly Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
Y/H	0.921	likely_pathogenic	0.9329	pathogenic	-1.997	Destabilizing	1.0	D	0.831	deleterious	D	0.69266989	None	None	N
Y/I	0.9579	likely_pathogenic	0.9493	pathogenic	-1.536	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
Y/K	0.996	likely_pathogenic	0.9959	pathogenic	-2.107	Highly Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
Y/L	0.9253	likely_pathogenic	0.9203	pathogenic	-1.536	Destabilizing	0.999	D	0.8	deleterious	None	None	None	None	N
Y/M	0.9594	likely_pathogenic	0.9559	pathogenic	-1.341	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
Y/N	0.9387	likely_pathogenic	0.9446	pathogenic	-2.897	Highly Destabilizing	1.0	D	0.835	deleterious	D	0.692468086	None	None	N
Y/P	0.9976	likely_pathogenic	0.998	pathogenic	-2.029	Highly Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
Y/Q	0.9924	likely_pathogenic	0.9922	pathogenic	-2.623	Highly Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
Y/R	0.9848	likely_pathogenic	0.9846	pathogenic	-1.911	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
Y/S	0.9296	likely_pathogenic	0.9341	pathogenic	-3.3	Highly Destabilizing	1.0	D	0.851	deleterious	D	0.69266989	None	None	N
Y/T	0.9752	likely_pathogenic	0.9731	pathogenic	-2.96	Highly Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
Y/V	0.8873	likely_pathogenic	0.8643	pathogenic	-2.029	Highly Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
Y/W	0.6767	likely_pathogenic	0.7356	pathogenic	-0.29	Destabilizing	1.0	D	0.811	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.