TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19868	59827;59828;59829	chr2:178592403;178592402;178592401	chr2:179457130;179457129;179457128
N2AB	18227	54904;54905;54906	chr2:178592403;178592402;178592401	chr2:179457130;179457129;179457128
N2A	17300	52123;52124;52125	chr2:178592403;178592402;178592401	chr2:179457130;179457129;179457128
N2B	10803	32632;32633;32634	chr2:178592403;178592402;178592401	chr2:179457130;179457129;179457128
Novex-1	10928	33007;33008;33009	chr2:178592403;178592402;178592401	chr2:179457130;179457129;179457128
Novex-2	10995	33208;33209;33210	chr2:178592403;178592402;178592401	chr2:179457130;179457129;179457128
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: Ig-119
• Domain position: 79
• Structural Position: 169
• Q(SASA): 0.12
• 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	None	None	0.954	N	0.638	0.279	0.604005332458	gnomAD-4.0.0	6.84559E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99651E-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	0.3397	likely_benign	0.3005	benign	-0.654	Destabilizing	0.044	N	0.271	neutral	N	0.401222849	None	None	N
V/C	0.8603	likely_pathogenic	0.8645	pathogenic	-0.763	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
V/D	0.9371	likely_pathogenic	0.9344	pathogenic	-0.111	Destabilizing	0.994	D	0.832	deleterious	D	0.532019394	None	None	N
V/E	0.8757	likely_pathogenic	0.8813	pathogenic	-0.193	Destabilizing	0.996	D	0.801	deleterious	None	None	None	None	N
V/F	0.4853	ambiguous	0.4841	ambiguous	-0.747	Destabilizing	0.998	D	0.804	deleterious	D	0.52563214	None	None	N
V/G	0.6411	likely_pathogenic	0.6459	pathogenic	-0.838	Destabilizing	0.925	D	0.775	deleterious	N	0.510009326	None	None	N
V/H	0.9437	likely_pathogenic	0.9488	pathogenic	-0.391	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
V/I	0.1244	likely_benign	0.1161	benign	-0.304	Destabilizing	0.954	D	0.638	neutral	N	0.483708159	None	None	N
V/K	0.8902	likely_pathogenic	0.8994	pathogenic	-0.465	Destabilizing	0.991	D	0.807	deleterious	None	None	None	None	N
V/L	0.5127	ambiguous	0.5169	ambiguous	-0.304	Destabilizing	0.91	D	0.628	neutral	N	0.506430303	None	None	N
V/M	0.4076	ambiguous	0.3869	ambiguous	-0.368	Destabilizing	0.999	D	0.729	prob.delet.	None	None	None	None	N
V/N	0.8734	likely_pathogenic	0.8615	pathogenic	-0.223	Destabilizing	0.999	D	0.851	deleterious	None	None	None	None	N
V/P	0.9885	likely_pathogenic	0.9918	pathogenic	-0.384	Destabilizing	0.996	D	0.799	deleterious	None	None	None	None	N
V/Q	0.8443	likely_pathogenic	0.85	pathogenic	-0.419	Destabilizing	0.999	D	0.816	deleterious	None	None	None	None	N
V/R	0.8491	likely_pathogenic	0.8683	pathogenic	-0.006	Destabilizing	0.996	D	0.848	deleterious	None	None	None	None	N
V/S	0.6545	likely_pathogenic	0.6284	pathogenic	-0.693	Destabilizing	0.942	D	0.744	deleterious	None	None	None	None	N
V/T	0.485	ambiguous	0.4608	ambiguous	-0.658	Destabilizing	0.97	D	0.669	neutral	None	None	None	None	N
V/W	0.9766	likely_pathogenic	0.9806	pathogenic	-0.822	Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	N
V/Y	0.87	likely_pathogenic	0.8851	pathogenic	-0.515	Destabilizing	0.999	D	0.794	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.