TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5711	17356;17357;17358	chr2:178731744;178731743;178731742	chr2:179596471;179596470;179596469
N2AB	5394	16405;16406;16407	chr2:178731744;178731743;178731742	chr2:179596471;179596470;179596469
N2A	4467	13624;13625;13626	chr2:178731744;178731743;178731742	chr2:179596471;179596470;179596469
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-40
• Domain position: 75
• Structural Position: 158
• Q(SASA): 0.062
• 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/L	None	None	0.76	D	0.625	0.376	0.446715556694	gnomAD-4.0.0	6.84258E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99509E-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	0.4071	ambiguous	0.3771	ambiguous	-2.392	Highly Destabilizing	0.046	N	0.329	neutral	N	0.416936089	None	None	N
V/C	0.9444	likely_pathogenic	0.9343	pathogenic	-2.189	Highly Destabilizing	0.998	D	0.839	deleterious	None	None	None	None	N
V/D	0.9947	likely_pathogenic	0.9933	pathogenic	-2.93	Highly Destabilizing	0.993	D	0.869	deleterious	None	None	None	None	N
V/E	0.9858	likely_pathogenic	0.9818	pathogenic	-2.663	Highly Destabilizing	0.982	D	0.843	deleterious	D	0.532116553	None	None	N
V/F	0.8309	likely_pathogenic	0.8214	pathogenic	-1.38	Destabilizing	0.993	D	0.841	deleterious	None	None	None	None	N
V/G	0.7181	likely_pathogenic	0.6755	pathogenic	-2.98	Highly Destabilizing	0.964	D	0.793	deleterious	N	0.499769157	None	None	N
V/H	0.9968	likely_pathogenic	0.9958	pathogenic	-2.641	Highly Destabilizing	0.999	D	0.868	deleterious	None	None	None	None	N
V/I	0.1293	likely_benign	0.1335	benign	-0.717	Destabilizing	0.893	D	0.554	neutral	None	None	None	None	N
V/K	0.9935	likely_pathogenic	0.9911	pathogenic	-1.9	Destabilizing	0.986	D	0.849	deleterious	None	None	None	None	N
V/L	0.586	likely_pathogenic	0.5883	pathogenic	-0.717	Destabilizing	0.76	D	0.625	neutral	D	0.538566938	None	None	N
V/M	0.6217	likely_pathogenic	0.606	pathogenic	-1.029	Destabilizing	0.997	D	0.759	deleterious	D	0.531863063	None	None	N
V/N	0.9852	likely_pathogenic	0.9815	pathogenic	-2.37	Highly Destabilizing	0.993	D	0.881	deleterious	None	None	None	None	N
V/P	0.9942	likely_pathogenic	0.9928	pathogenic	-1.252	Destabilizing	0.993	D	0.862	deleterious	None	None	None	None	N
V/Q	0.9857	likely_pathogenic	0.981	pathogenic	-2.132	Highly Destabilizing	0.993	D	0.871	deleterious	None	None	None	None	N
V/R	0.986	likely_pathogenic	0.9811	pathogenic	-1.822	Destabilizing	0.993	D	0.875	deleterious	None	None	None	None	N
V/S	0.8603	likely_pathogenic	0.8355	pathogenic	-3.052	Highly Destabilizing	0.973	D	0.799	deleterious	None	None	None	None	N
V/T	0.757	likely_pathogenic	0.7399	pathogenic	-2.623	Highly Destabilizing	0.953	D	0.649	neutral	None	None	None	None	N
V/W	0.9978	likely_pathogenic	0.9972	pathogenic	-1.841	Destabilizing	0.999	D	0.848	deleterious	None	None	None	None	N
V/Y	0.9872	likely_pathogenic	0.9824	pathogenic	-1.522	Destabilizing	0.998	D	0.841	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.