TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31391	94396;94397;94398	chr2:178547455;178547454;178547453	chr2:179412182;179412181;179412180
N2AB	29750	89473;89474;89475	chr2:178547455;178547454;178547453	chr2:179412182;179412181;179412180
N2A	28823	86692;86693;86694	chr2:178547455;178547454;178547453	chr2:179412182;179412181;179412180
N2B	22326	67201;67202;67203	chr2:178547455;178547454;178547453	chr2:179412182;179412181;179412180
Novex-1	22451	67576;67577;67578	chr2:178547455;178547454;178547453	chr2:179412182;179412181;179412180
Novex-2	22518	67777;67778;67779	chr2:178547455;178547454;178547453	chr2:179412182;179412181;179412180
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Fn3-116
• Domain position: 84
• Structural Position: 117
• Q(SASA): 0.3815
• Predicted PPI site: I

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
V/I	None	None	0.039	N	0.27	0.12	0.320256813643	gnomAD-4.0.0	6.85386E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.00584E-07	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
V/A	0.5833	likely_pathogenic	0.4637	ambiguous	-1.168	Destabilizing	0.928	D	0.614	neutral	N	0.506955086	None	None	I
V/C	0.889	likely_pathogenic	0.8287	pathogenic	-1.08	Destabilizing	0.999	D	0.755	deleterious	None	None	None	None	I
V/D	0.8864	likely_pathogenic	0.8296	pathogenic	-1.012	Destabilizing	0.996	D	0.806	deleterious	N	0.515747928	None	None	I
V/E	0.7616	likely_pathogenic	0.6687	pathogenic	-1.081	Destabilizing	0.997	D	0.784	deleterious	None	None	None	None	I
V/F	0.4172	ambiguous	0.3561	ambiguous	-1.251	Destabilizing	0.978	D	0.769	deleterious	N	0.470456959	None	None	I
V/G	0.6602	likely_pathogenic	0.5404	ambiguous	-1.373	Destabilizing	0.989	D	0.774	deleterious	N	0.478152733	None	None	I
V/H	0.9124	likely_pathogenic	0.8484	pathogenic	-0.783	Destabilizing	0.999	D	0.807	deleterious	None	None	None	None	I
V/I	0.0732	likely_benign	0.0725	benign	-0.738	Destabilizing	0.039	N	0.27	neutral	N	0.448408215	None	None	I
V/K	0.7239	likely_pathogenic	0.6346	pathogenic	-0.753	Destabilizing	0.992	D	0.793	deleterious	None	None	None	None	I
V/L	0.452	ambiguous	0.3648	ambiguous	-0.738	Destabilizing	0.476	N	0.559	neutral	N	0.453544676	None	None	I
V/M	0.3125	likely_benign	0.2452	benign	-0.585	Destabilizing	0.983	D	0.797	deleterious	None	None	None	None	I
V/N	0.7273	likely_pathogenic	0.6254	pathogenic	-0.572	Destabilizing	0.997	D	0.811	deleterious	None	None	None	None	I
V/P	0.8842	likely_pathogenic	0.8225	pathogenic	-0.847	Destabilizing	0.997	D	0.814	deleterious	None	None	None	None	I
V/Q	0.715	likely_pathogenic	0.6007	pathogenic	-0.885	Destabilizing	0.997	D	0.812	deleterious	None	None	None	None	I
V/R	0.6859	likely_pathogenic	0.5947	pathogenic	-0.182	Destabilizing	0.997	D	0.808	deleterious	None	None	None	None	I
V/S	0.6784	likely_pathogenic	0.5428	ambiguous	-1.066	Destabilizing	0.992	D	0.783	deleterious	None	None	None	None	I
V/T	0.4864	ambiguous	0.4061	ambiguous	-1.033	Destabilizing	0.944	D	0.731	prob.delet.	None	None	None	None	I
V/W	0.9604	likely_pathogenic	0.9387	pathogenic	-1.275	Destabilizing	0.999	D	0.799	deleterious	None	None	None	None	I
V/Y	0.8449	likely_pathogenic	0.7728	pathogenic	-0.967	Destabilizing	0.992	D	0.781	deleterious	None	None	None	None	I

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.