TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16129	48610;48611;48612	chr2:178615716;178615715;178615714	chr2:179480443;179480442;179480441
N2AB	14488	43687;43688;43689	chr2:178615716;178615715;178615714	chr2:179480443;179480442;179480441
N2A	13561	40906;40907;40908	chr2:178615716;178615715;178615714	chr2:179480443;179480442;179480441
N2B	7064	21415;21416;21417	chr2:178615716;178615715;178615714	chr2:179480443;179480442;179480441
Novex-1	7189	21790;21791;21792	chr2:178615716;178615715;178615714	chr2:179480443;179480442;179480441
Novex-2	7256	21991;21992;21993	chr2:178615716;178615715;178615714	chr2:179480443;179480442;179480441
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-4
• Domain position: 75
• Structural Position: 108
• Q(SASA): 0.091
• 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	rs756510403	-0.888	0.997	N	0.612	0.433	0.78358005052	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	6.48E-05	0	None	0	0	None	0	None	0	0	0
V/I	rs756510403	-0.888	0.997	N	0.612	0.433	0.78358005052	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
V/I	rs756510403	-0.888	0.997	N	0.612	0.433	0.78358005052	gnomAD-4.0.0	2.56674E-06	None	None	None	None	N	None	3.3896E-05	0	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
V/A	0.8801	likely_pathogenic	0.8861	pathogenic	-2.6	Highly Destabilizing	0.999	D	0.627	neutral	D	0.798318627	None	None	N
V/C	0.9781	likely_pathogenic	0.9797	pathogenic	-2.171	Highly Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
V/D	0.9978	likely_pathogenic	0.997	pathogenic	-3.684	Highly Destabilizing	1.0	D	0.888	deleterious	D	0.832706966	None	None	N
V/E	0.9942	likely_pathogenic	0.9927	pathogenic	-3.383	Highly Destabilizing	1.0	D	0.872	deleterious	None	None	None	None	N
V/F	0.9241	likely_pathogenic	0.9146	pathogenic	-1.488	Destabilizing	1.0	D	0.805	deleterious	D	0.8316582	None	None	N
V/G	0.9192	likely_pathogenic	0.9153	pathogenic	-3.17	Highly Destabilizing	1.0	D	0.877	deleterious	D	0.832706966	None	None	N
V/H	0.9988	likely_pathogenic	0.9986	pathogenic	-2.972	Highly Destabilizing	1.0	D	0.872	deleterious	None	None	None	None	N
V/I	0.1365	likely_benign	0.1345	benign	-0.93	Destabilizing	0.997	D	0.612	neutral	N	0.5129903	None	None	N
V/K	0.9963	likely_pathogenic	0.9955	pathogenic	-2.29	Highly Destabilizing	1.0	D	0.872	deleterious	None	None	None	None	N
V/L	0.8061	likely_pathogenic	0.8001	pathogenic	-0.93	Destabilizing	0.997	D	0.644	neutral	D	0.667064187	None	None	N
V/M	0.8814	likely_pathogenic	0.8816	pathogenic	-1.193	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
V/N	0.9936	likely_pathogenic	0.992	pathogenic	-2.932	Highly Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
V/P	0.9961	likely_pathogenic	0.9944	pathogenic	-1.472	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
V/Q	0.9952	likely_pathogenic	0.9945	pathogenic	-2.627	Highly Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
V/R	0.9918	likely_pathogenic	0.9907	pathogenic	-2.236	Highly Destabilizing	1.0	D	0.902	deleterious	None	None	None	None	N
V/S	0.9747	likely_pathogenic	0.9727	pathogenic	-3.424	Highly Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
V/T	0.9365	likely_pathogenic	0.9332	pathogenic	-2.981	Highly Destabilizing	0.999	D	0.659	neutral	None	None	None	None	N
V/W	0.9991	likely_pathogenic	0.999	pathogenic	-2.076	Highly Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
V/Y	0.9921	likely_pathogenic	0.9908	pathogenic	-1.804	Destabilizing	1.0	D	0.813	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.