TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14684	44275;44276;44277	chr2:178630908;178630907;178630906	chr2:179495635;179495634;179495633
N2AB	13043	39352;39353;39354	chr2:178630908;178630907;178630906	chr2:179495635;179495634;179495633
N2A	12116	36571;36572;36573	chr2:178630908;178630907;178630906	chr2:179495635;179495634;179495633
N2B	5619	17080;17081;17082	chr2:178630908;178630907;178630906	chr2:179495635;179495634;179495633
Novex-1	5744	17455;17456;17457	chr2:178630908;178630907;178630906	chr2:179495635;179495634;179495633
Novex-2	5811	17656;17657;17658	chr2:178630908;178630907;178630906	chr2:179495635;179495634;179495633
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-98
• Domain position: 10
• Structural Position: 13
• Q(SASA): 0.1684
• 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	rs2059719746	None	0.959	N	0.438	0.225	0.327952845175	gnomAD-4.0.0	6.8445E-07	None	None	None	None	N	None	0	2.23804E-05	None	0	0	None	0	0	0	0	0
V/M	rs2059719746	None	0.959	N	0.404	0.296	0.347659731818	gnomAD-4.0.0	1.3689E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79931E-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	0.3115	likely_benign	0.2353	benign	-1.191	Destabilizing	0.991	D	0.504	neutral	N	0.427360412	None	None	N
V/C	0.8913	likely_pathogenic	0.8493	pathogenic	-0.842	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
V/D	0.8221	likely_pathogenic	0.7395	pathogenic	-0.816	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
V/E	0.5217	ambiguous	0.4539	ambiguous	-0.792	Destabilizing	1.0	D	0.844	deleterious	D	0.591220862	None	None	N
V/F	0.3785	ambiguous	0.3465	ambiguous	-0.806	Destabilizing	0.998	D	0.777	deleterious	None	None	None	None	N
V/G	0.6499	likely_pathogenic	0.5197	ambiguous	-1.522	Destabilizing	0.999	D	0.841	deleterious	D	0.592162524	None	None	N
V/H	0.8529	likely_pathogenic	0.8181	pathogenic	-1.059	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
V/I	0.0982	likely_benign	0.1001	benign	-0.385	Destabilizing	0.969	D	0.551	neutral	None	None	None	None	N
V/K	0.4897	ambiguous	0.4336	ambiguous	-1.036	Destabilizing	0.999	D	0.839	deleterious	None	None	None	None	N
V/L	0.3725	ambiguous	0.3519	ambiguous	-0.385	Destabilizing	0.959	D	0.438	neutral	N	0.459541886	None	None	N
V/M	0.1654	likely_benign	0.1591	benign	-0.39	Destabilizing	0.959	D	0.404	neutral	N	0.513159107	None	None	N
V/N	0.7199	likely_pathogenic	0.6572	pathogenic	-0.902	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
V/P	0.9841	likely_pathogenic	0.9665	pathogenic	-0.617	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
V/Q	0.4619	ambiguous	0.4229	ambiguous	-0.987	Destabilizing	0.999	D	0.862	deleterious	None	None	None	None	N
V/R	0.4619	ambiguous	0.3796	ambiguous	-0.63	Destabilizing	0.999	D	0.854	deleterious	None	None	None	None	N
V/S	0.5175	ambiguous	0.4214	ambiguous	-1.439	Destabilizing	0.999	D	0.827	deleterious	None	None	None	None	N
V/T	0.2711	likely_benign	0.2296	benign	-1.295	Destabilizing	0.997	D	0.589	neutral	None	None	None	None	N
V/W	0.9532	likely_pathogenic	0.9325	pathogenic	-1.038	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
V/Y	0.86	likely_pathogenic	0.83	pathogenic	-0.705	Destabilizing	1.0	D	0.78	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.