TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18903	56932;56933;56934	chr2:178599003;178599002;178599001	chr2:179463730;179463729;179463728
N2AB	17262	52009;52010;52011	chr2:178599003;178599002;178599001	chr2:179463730;179463729;179463728
N2A	16335	49228;49229;49230	chr2:178599003;178599002;178599001	chr2:179463730;179463729;179463728
N2B	9838	29737;29738;29739	chr2:178599003;178599002;178599001	chr2:179463730;179463729;179463728
Novex-1	9963	30112;30113;30114	chr2:178599003;178599002;178599001	chr2:179463730;179463729;179463728
Novex-2	10030	30313;30314;30315	chr2:178599003;178599002;178599001	chr2:179463730;179463729;179463728
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: Fn3-25
• Domain position: 20
• Structural Position: 22
• Q(SASA): 0.1385
• 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	0.997	N	0.639	0.319	0.435479573448	gnomAD-4.0.0	3.20077E-06	None	None	None	None	N	None	0	0	None	0	2.79673E-05	None	0	0	2.87213E-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	0.9212	likely_pathogenic	0.8979	pathogenic	-1.977	Destabilizing	0.999	D	0.607	neutral	N	0.501922663	None	None	N
V/C	0.9772	likely_pathogenic	0.9697	pathogenic	-1.835	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
V/D	0.9997	likely_pathogenic	0.9994	pathogenic	-2.587	Highly Destabilizing	1.0	D	0.884	deleterious	D	0.525813816	None	None	N
V/E	0.9983	likely_pathogenic	0.9975	pathogenic	-2.273	Highly Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	N
V/F	0.9694	likely_pathogenic	0.9654	pathogenic	-1.133	Destabilizing	1.0	D	0.736	prob.delet.	N	0.487830879	None	None	N
V/G	0.9816	likely_pathogenic	0.9714	pathogenic	-2.604	Highly Destabilizing	1.0	D	0.885	deleterious	D	0.525813816	None	None	N
V/H	0.9997	likely_pathogenic	0.9995	pathogenic	-2.592	Highly Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	N
V/I	0.0925	likely_benign	0.1047	benign	-0.175	Destabilizing	0.997	D	0.521	neutral	N	0.490542839	None	None	N
V/K	0.9989	likely_pathogenic	0.9982	pathogenic	-1.419	Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	N
V/L	0.481	ambiguous	0.5434	ambiguous	-0.175	Destabilizing	0.997	D	0.639	neutral	N	0.423789411	None	None	N
V/M	0.794	likely_pathogenic	0.8158	pathogenic	-0.654	Destabilizing	1.0	D	0.734	prob.delet.	None	None	None	None	N
V/N	0.9986	likely_pathogenic	0.9977	pathogenic	-2.027	Highly Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
V/P	0.9987	likely_pathogenic	0.9975	pathogenic	-0.753	Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	N
V/Q	0.9982	likely_pathogenic	0.9972	pathogenic	-1.658	Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
V/R	0.9977	likely_pathogenic	0.9961	pathogenic	-1.667	Destabilizing	1.0	D	0.908	deleterious	None	None	None	None	N
V/S	0.9934	likely_pathogenic	0.9895	pathogenic	-2.661	Highly Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
V/T	0.9671	likely_pathogenic	0.9565	pathogenic	-2.165	Highly Destabilizing	0.999	D	0.609	neutral	None	None	None	None	N
V/W	0.9997	likely_pathogenic	0.9996	pathogenic	-1.632	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
V/Y	0.9985	likely_pathogenic	0.9979	pathogenic	-1.253	Destabilizing	1.0	D	0.738	prob.delet.	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.