TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3843	11752;11753;11754	chr2:178741706;178741705;178741704	chr2:179606433;179606432;179606431
N2AB	3526	10801;10802;10803	chr2:178741706;178741705;178741704	chr2:179606433;179606432;179606431
N2A	None	None	chr2:None	chr2:None
N2B	3480	10663;10664;10665	chr2:178741706;178741705;178741704	chr2:179606433;179606432;179606431
Novex-1	3605	11038;11039;11040	chr2:178741706;178741705;178741704	chr2:179606433;179606432;179606431
Novex-2	3672	11239;11240;11241	chr2:178741706;178741705;178741704	chr2:179606433;179606432;179606431
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-27
• Domain position: 24
• Structural Position: 35
• Q(SASA): 0.058
• 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	rs766747906	-2.714	0.002	D	0.303	0.19	None	gnomAD-2.1.1	2.14E-05	None	None	None	None	N	None	0	0	None	0	3.07913E-04	None	0	None	0	0	0
V/A	rs766747906	-2.714	0.002	D	0.303	0.19	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	1.92827E-04	None	0	0	0	0	0
V/A	rs766747906	-2.714	0.002	D	0.303	0.19	None	gnomAD-4.0.0	3.84354E-06	None	None	None	None	N	None	0	0	None	0	7.27555E-05	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	0.2009	likely_benign	0.239	benign	-2.302	Highly Destabilizing	0.002	N	0.303	neutral	D	0.524132127	None	None	N
V/C	0.8345	likely_pathogenic	0.8706	pathogenic	-1.844	Destabilizing	0.947	D	0.848	deleterious	None	None	None	None	N
V/D	0.938	likely_pathogenic	0.958	pathogenic	-3.311	Highly Destabilizing	0.638	D	0.869	deleterious	D	0.731864203	None	None	N
V/E	0.8896	likely_pathogenic	0.9155	pathogenic	-3.054	Highly Destabilizing	0.7	D	0.848	deleterious	None	None	None	None	N
V/F	0.6189	likely_pathogenic	0.5889	pathogenic	-1.197	Destabilizing	0.781	D	0.846	deleterious	D	0.599056229	None	None	N
V/G	0.4911	ambiguous	0.5475	ambiguous	-2.841	Highly Destabilizing	0.468	N	0.807	deleterious	D	0.753626676	None	None	N
V/H	0.9739	likely_pathogenic	0.9798	pathogenic	-2.665	Highly Destabilizing	0.982	D	0.879	deleterious	None	None	None	None	N
V/I	0.1369	likely_benign	0.1175	benign	-0.755	Destabilizing	0.172	N	0.572	neutral	N	0.520030425	None	None	N
V/K	0.938	likely_pathogenic	0.955	pathogenic	-1.932	Destabilizing	0.7	D	0.851	deleterious	None	None	None	None	N
V/L	0.5133	ambiguous	0.4541	ambiguous	-0.755	Destabilizing	0.094	N	0.638	neutral	D	0.624881722	None	None	N
V/M	0.3612	ambiguous	0.3248	benign	-0.959	Destabilizing	0.826	D	0.74	deleterious	None	None	None	None	N
V/N	0.8767	likely_pathogenic	0.8996	pathogenic	-2.413	Highly Destabilizing	0.826	D	0.877	deleterious	None	None	None	None	N
V/P	0.9651	likely_pathogenic	0.9706	pathogenic	-1.251	Destabilizing	0.7	D	0.862	deleterious	None	None	None	None	N
V/Q	0.9092	likely_pathogenic	0.93	pathogenic	-2.168	Highly Destabilizing	0.826	D	0.867	deleterious	None	None	None	None	N
V/R	0.8975	likely_pathogenic	0.9266	pathogenic	-1.823	Destabilizing	0.7	D	0.869	deleterious	None	None	None	None	N
V/S	0.4919	ambiguous	0.5528	ambiguous	-2.923	Highly Destabilizing	0.539	D	0.815	deleterious	None	None	None	None	N
V/T	0.3847	ambiguous	0.4291	ambiguous	-2.538	Highly Destabilizing	0.25	N	0.673	neutral	None	None	None	None	N
V/W	0.9879	likely_pathogenic	0.9899	pathogenic	-1.838	Destabilizing	0.982	D	0.857	deleterious	None	None	None	None	N
V/Y	0.9412	likely_pathogenic	0.9486	pathogenic	-1.523	Destabilizing	0.826	D	0.844	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.