TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20500	61723;61724;61725	chr2:178590227;178590226;178590225	chr2:179454954;179454953;179454952
N2AB	18859	56800;56801;56802	chr2:178590227;178590226;178590225	chr2:179454954;179454953;179454952
N2A	17932	54019;54020;54021	chr2:178590227;178590226;178590225	chr2:179454954;179454953;179454952
N2B	11435	34528;34529;34530	chr2:178590227;178590226;178590225	chr2:179454954;179454953;179454952
Novex-1	11560	34903;34904;34905	chr2:178590227;178590226;178590225	chr2:179454954;179454953;179454952
Novex-2	11627	35104;35105;35106	chr2:178590227;178590226;178590225	chr2:179454954;179454953;179454952
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-121
• Domain position: 22
• Structural Position: 35
• Q(SASA): 0.173
• 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	0.369	D	0.545	0.44	0.546521485473	gnomAD-4.0.0	1.63546E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.92754E-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	0.7833	likely_pathogenic	0.8279	pathogenic	-1.562	Destabilizing	0.892	D	0.577	neutral	N	0.480350928	None	None	N
V/C	0.9361	likely_pathogenic	0.9368	pathogenic	-1.039	Destabilizing	0.999	D	0.803	deleterious	None	None	None	None	N
V/D	0.9968	likely_pathogenic	0.9985	pathogenic	-1.61	Destabilizing	0.994	D	0.843	deleterious	D	0.598766493	None	None	N
V/E	0.9884	likely_pathogenic	0.9937	pathogenic	-1.541	Destabilizing	0.996	D	0.827	deleterious	None	None	None	None	N
V/F	0.8204	likely_pathogenic	0.8698	pathogenic	-1.053	Destabilizing	0.967	D	0.812	deleterious	D	0.570011229	None	None	N
V/G	0.8611	likely_pathogenic	0.9004	pathogenic	-1.945	Destabilizing	0.983	D	0.84	deleterious	D	0.573228381	None	None	N
V/H	0.9965	likely_pathogenic	0.9979	pathogenic	-1.54	Destabilizing	0.999	D	0.854	deleterious	None	None	None	None	N
V/I	0.1244	likely_benign	0.1275	benign	-0.58	Destabilizing	0.025	N	0.196	neutral	N	0.459068792	None	None	N
V/K	0.9907	likely_pathogenic	0.995	pathogenic	-1.483	Destabilizing	0.987	D	0.827	deleterious	None	None	None	None	N
V/L	0.6832	likely_pathogenic	0.763	pathogenic	-0.58	Destabilizing	0.369	N	0.545	neutral	D	0.531015493	None	None	N
V/M	0.7076	likely_pathogenic	0.7888	pathogenic	-0.479	Destabilizing	0.975	D	0.743	deleterious	None	None	None	None	N
V/N	0.9896	likely_pathogenic	0.9943	pathogenic	-1.394	Destabilizing	0.996	D	0.863	deleterious	None	None	None	None	N
V/P	0.9891	likely_pathogenic	0.9926	pathogenic	-0.874	Destabilizing	0.996	D	0.827	deleterious	None	None	None	None	N
V/Q	0.9857	likely_pathogenic	0.9915	pathogenic	-1.448	Destabilizing	0.996	D	0.842	deleterious	None	None	None	None	N
V/R	0.9836	likely_pathogenic	0.9904	pathogenic	-1.059	Destabilizing	0.996	D	0.861	deleterious	None	None	None	None	N
V/S	0.9408	likely_pathogenic	0.9603	pathogenic	-1.907	Destabilizing	0.987	D	0.818	deleterious	None	None	None	None	N
V/T	0.8601	likely_pathogenic	0.8997	pathogenic	-1.717	Destabilizing	0.916	D	0.672	neutral	None	None	None	None	N
V/W	0.9963	likely_pathogenic	0.9975	pathogenic	-1.363	Destabilizing	0.999	D	0.83	deleterious	None	None	None	None	N
V/Y	0.9821	likely_pathogenic	0.9865	pathogenic	-1.029	Destabilizing	0.987	D	0.805	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.