TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31584	94975;94976;94977	chr2:178546678;178546677;178546676	chr2:179411405;179411404;179411403
N2AB	29943	90052;90053;90054	chr2:178546678;178546677;178546676	chr2:179411405;179411404;179411403
N2A	29016	87271;87272;87273	chr2:178546678;178546677;178546676	chr2:179411405;179411404;179411403
N2B	22519	67780;67781;67782	chr2:178546678;178546677;178546676	chr2:179411405;179411404;179411403
Novex-1	22644	68155;68156;68157	chr2:178546678;178546677;178546676	chr2:179411405;179411404;179411403
Novex-2	22711	68356;68357;68358	chr2:178546678;178546677;178546676	chr2:179411405;179411404;179411403
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: Fn3-118
• Domain position: 79
• Structural Position: 108
• Q(SASA): 0.0507
• 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/A	rs1224689157	-2.893	0.928	D	0.675	0.671	0.753032484505	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
V/A	rs1224689157	-2.893	0.928	D	0.675	0.671	0.753032484505	gnomAD-4.0.0	1.59139E-06	None	None	None	None	N	None	5.65483E-05	0	None	0	0	None	0	0	0	0	0
V/M	None	None	0.978	D	0.846	0.594	0.597040176542	gnomAD-4.0.0	1.59139E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8586E-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
V/A	0.8508	likely_pathogenic	0.8378	pathogenic	-2.567	Highly Destabilizing	0.928	D	0.675	prob.neutral	D	0.559885727	None	None	N
V/C	0.9614	likely_pathogenic	0.9593	pathogenic	-2.047	Highly Destabilizing	0.999	D	0.871	deleterious	None	None	None	None	N
V/D	0.9992	likely_pathogenic	0.999	pathogenic	-3.427	Highly Destabilizing	0.997	D	0.944	deleterious	None	None	None	None	N
V/E	0.9975	likely_pathogenic	0.9966	pathogenic	-3.115	Highly Destabilizing	0.996	D	0.933	deleterious	D	0.655950436	None	None	N
V/F	0.9563	likely_pathogenic	0.9522	pathogenic	-1.351	Destabilizing	0.983	D	0.899	deleterious	None	None	None	None	N
V/G	0.9585	likely_pathogenic	0.9555	pathogenic	-3.159	Highly Destabilizing	0.989	D	0.944	deleterious	D	0.655950436	None	None	N
V/H	0.9993	likely_pathogenic	0.9991	pathogenic	-2.925	Highly Destabilizing	0.999	D	0.92	deleterious	None	None	None	None	N
V/I	0.1133	likely_benign	0.104	benign	-0.836	Destabilizing	0.05	N	0.375	neutral	None	None	None	None	N
V/K	0.9985	likely_pathogenic	0.9982	pathogenic	-1.974	Destabilizing	0.992	D	0.934	deleterious	None	None	None	None	N
V/L	0.782	likely_pathogenic	0.7474	pathogenic	-0.836	Destabilizing	0.476	N	0.631	neutral	D	0.529331849	None	None	N
V/M	0.8871	likely_pathogenic	0.8728	pathogenic	-1.201	Destabilizing	0.978	D	0.846	deleterious	D	0.560139217	None	None	N
V/N	0.9961	likely_pathogenic	0.9949	pathogenic	-2.621	Highly Destabilizing	0.997	D	0.943	deleterious	None	None	None	None	N
V/P	0.9964	likely_pathogenic	0.9943	pathogenic	-1.396	Destabilizing	0.997	D	0.937	deleterious	None	None	None	None	N
V/Q	0.9969	likely_pathogenic	0.9962	pathogenic	-2.277	Highly Destabilizing	0.997	D	0.939	deleterious	None	None	None	None	N
V/R	0.9959	likely_pathogenic	0.9954	pathogenic	-2.017	Highly Destabilizing	0.997	D	0.946	deleterious	None	None	None	None	N
V/S	0.9709	likely_pathogenic	0.9678	pathogenic	-3.142	Highly Destabilizing	0.992	D	0.932	deleterious	None	None	None	None	N
V/T	0.9431	likely_pathogenic	0.9413	pathogenic	-2.679	Highly Destabilizing	0.944	D	0.759	deleterious	None	None	None	None	N
V/W	0.9996	likely_pathogenic	0.9995	pathogenic	-1.891	Destabilizing	0.999	D	0.905	deleterious	None	None	None	None	N
V/Y	0.9967	likely_pathogenic	0.9962	pathogenic	-1.638	Destabilizing	0.992	D	0.897	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.