TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6253	18982;18983;18984	chr2:178729399;178729398;178729397	chr2:179594126;179594125;179594124
N2AB	5936	18031;18032;18033	chr2:178729399;178729398;178729397	chr2:179594126;179594125;179594124
N2A	5009	15250;15251;15252	chr2:178729399;178729398;178729397	chr2:179594126;179594125;179594124
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-46
• Domain position: 55
• Structural Position: 135
• Q(SASA): 0.1897
• 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/G	rs1236936612	-2.527	0.642	N	0.651	0.32	0.8362503026	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
V/G	rs1236936612	-2.527	0.642	N	0.651	0.32	0.8362503026	gnomAD-4.0.0	1.59159E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43271E-05	0
V/L	rs754852812	None	0.002	N	0.183	0.104	0.462200489575	gnomAD-4.0.0	2.25809E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.87855E-05	0	1.65678E-05

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	0.1329	likely_benign	0.1463	benign	-1.649	Destabilizing	0.01	N	0.213	neutral	N	0.497136029	None	None	N
V/C	0.5497	ambiguous	0.625	pathogenic	-1.212	Destabilizing	0.995	D	0.604	neutral	None	None	None	None	N
V/D	0.2418	likely_benign	0.2575	benign	-1.833	Destabilizing	0.543	D	0.683	prob.neutral	None	None	None	None	N
V/E	0.1884	likely_benign	0.1943	benign	-1.813	Destabilizing	0.006	N	0.55	neutral	N	0.469159994	None	None	N
V/F	0.1084	likely_benign	0.1131	benign	-1.282	Destabilizing	0.893	D	0.659	neutral	None	None	None	None	N
V/G	0.1601	likely_benign	0.166	benign	-1.983	Destabilizing	0.642	D	0.651	neutral	N	0.473856525	None	None	N
V/H	0.3175	likely_benign	0.3493	ambiguous	-1.513	Destabilizing	0.985	D	0.638	neutral	None	None	None	None	N
V/I	0.0684	likely_benign	0.0706	benign	-0.813	Destabilizing	0.007	N	0.197	neutral	None	None	None	None	N
V/K	0.1965	likely_benign	0.2128	benign	-1.269	Destabilizing	0.543	D	0.622	neutral	None	None	None	None	N
V/L	0.1146	likely_benign	0.1234	benign	-0.813	Destabilizing	0.002	N	0.183	neutral	N	0.431124468	None	None	N
V/M	0.0991	likely_benign	0.1074	benign	-0.667	Destabilizing	0.863	D	0.575	neutral	N	0.50023505	None	None	N
V/N	0.1593	likely_benign	0.1889	benign	-1.149	Destabilizing	0.893	D	0.7	prob.neutral	None	None	None	None	N
V/P	0.7214	likely_pathogenic	0.74	pathogenic	-1.059	Destabilizing	0.944	D	0.673	neutral	None	None	None	None	N
V/Q	0.1967	likely_benign	0.2109	benign	-1.333	Destabilizing	0.807	D	0.667	neutral	None	None	None	None	N
V/R	0.1665	likely_benign	0.1646	benign	-0.773	Destabilizing	0.893	D	0.696	prob.neutral	None	None	None	None	N
V/S	0.1351	likely_benign	0.1502	benign	-1.677	Destabilizing	0.329	N	0.599	neutral	None	None	None	None	N
V/T	0.1194	likely_benign	0.1359	benign	-1.551	Destabilizing	0.013	N	0.193	neutral	None	None	None	None	N
V/W	0.5937	likely_pathogenic	0.5996	pathogenic	-1.503	Destabilizing	0.995	D	0.665	neutral	None	None	None	None	N
V/Y	0.3166	likely_benign	0.3382	benign	-1.201	Destabilizing	0.944	D	0.637	neutral	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.