TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17541	52846;52847;52848	chr2:178608262;178608261;178608260	chr2:179472989;179472988;179472987
N2AB	15900	47923;47924;47925	chr2:178608262;178608261;178608260	chr2:179472989;179472988;179472987
N2A	14973	45142;45143;45144	chr2:178608262;178608261;178608260	chr2:179472989;179472988;179472987
N2B	8476	25651;25652;25653	chr2:178608262;178608261;178608260	chr2:179472989;179472988;179472987
Novex-1	8601	26026;26027;26028	chr2:178608262;178608261;178608260	chr2:179472989;179472988;179472987
Novex-2	8668	26227;26228;26229	chr2:178608262;178608261;178608260	chr2:179472989;179472988;179472987
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: Fn3-15
• Domain position: 72
• Structural Position: 105
• Q(SASA): 0.0832
• 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
V/I	rs772579140	-0.908	0.011	N	0.201	0.072	0.391470661076	gnomAD-2.1.1	4.07E-06	None	None	None	None	N	None	0	0	None	0	5.69E-05	None	0	None	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
V/A	0.5509	ambiguous	0.4771	ambiguous	-1.878	Destabilizing	0.78	D	0.658	neutral	N	0.481520711	None	None	N
V/C	0.838	likely_pathogenic	0.8056	pathogenic	-1.071	Destabilizing	0.999	D	0.768	deleterious	None	None	None	None	N
V/D	0.9339	likely_pathogenic	0.8796	pathogenic	-2.625	Highly Destabilizing	0.995	D	0.864	deleterious	N	0.455104901	None	None	N
V/E	0.6978	likely_pathogenic	0.5917	pathogenic	-2.354	Highly Destabilizing	0.996	D	0.803	deleterious	None	None	None	None	N
V/F	0.4816	ambiguous	0.3926	ambiguous	-1.013	Destabilizing	0.968	D	0.775	deleterious	N	0.475384172	None	None	N
V/G	0.787	likely_pathogenic	0.7232	pathogenic	-2.427	Highly Destabilizing	0.995	D	0.835	deleterious	N	0.466786882	None	None	N
V/H	0.9159	likely_pathogenic	0.8672	pathogenic	-2.383	Highly Destabilizing	0.999	D	0.861	deleterious	None	None	None	None	N
V/I	0.0696	likely_benign	0.0672	benign	-0.31	Destabilizing	0.011	N	0.201	neutral	N	0.409679255	None	None	N
V/K	0.8805	likely_pathogenic	0.8199	pathogenic	-1.338	Destabilizing	0.988	D	0.804	deleterious	None	None	None	None	N
V/L	0.3211	likely_benign	0.269	benign	-0.31	Destabilizing	0.437	N	0.444	neutral	N	0.449005648	None	None	N
V/M	0.257	likely_benign	0.2155	benign	-0.424	Destabilizing	0.976	D	0.717	prob.delet.	None	None	None	None	N
V/N	0.7583	likely_pathogenic	0.6811	pathogenic	-1.826	Destabilizing	0.996	D	0.885	deleterious	None	None	None	None	N
V/P	0.9938	likely_pathogenic	0.9915	pathogenic	-0.811	Destabilizing	0.996	D	0.799	deleterious	None	None	None	None	N
V/Q	0.6686	likely_pathogenic	0.5829	pathogenic	-1.543	Destabilizing	0.996	D	0.832	deleterious	None	None	None	None	N
V/R	0.8377	likely_pathogenic	0.7636	pathogenic	-1.425	Destabilizing	0.996	D	0.882	deleterious	None	None	None	None	N
V/S	0.6081	likely_pathogenic	0.5175	ambiguous	-2.333	Highly Destabilizing	0.988	D	0.766	deleterious	None	None	None	None	N
V/T	0.4433	ambiguous	0.3819	ambiguous	-1.925	Destabilizing	0.919	D	0.684	prob.neutral	None	None	None	None	N
V/W	0.9722	likely_pathogenic	0.9551	pathogenic	-1.629	Destabilizing	0.999	D	0.819	deleterious	None	None	None	None	N
V/Y	0.8584	likely_pathogenic	0.8074	pathogenic	-1.215	Destabilizing	0.996	D	0.781	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.