TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31438	94537;94538;94539	chr2:178547213;178547212;178547211	chr2:179411940;179411939;179411938
N2AB	29797	89614;89615;89616	chr2:178547213;178547212;178547211	chr2:179411940;179411939;179411938
N2A	28870	86833;86834;86835	chr2:178547213;178547212;178547211	chr2:179411940;179411939;179411938
N2B	22373	67342;67343;67344	chr2:178547213;178547212;178547211	chr2:179411940;179411939;179411938
Novex-1	22498	67717;67718;67719	chr2:178547213;178547212;178547211	chr2:179411940;179411939;179411938
Novex-2	22565	67918;67919;67920	chr2:178547213;178547212;178547211	chr2:179411940;179411939;179411938
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Fn3-117
• Domain position: 31
• Structural Position: 33
• Q(SASA): 0.2667
• Predicted PPI site: I

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
S/N	rs769930510	-0.418	0.999	N	0.73	0.367	0.297718772494	gnomAD-2.1.1	8.04E-06	None	None	None	None	I	None	0	5.79E-05	None	0	0	None	0	None	0	0	0
S/N	rs769930510	-0.418	0.999	N	0.73	0.367	0.297718772494	gnomAD-4.0.0	2.05264E-06	None	None	None	None	I	None	0	4.47227E-05	None	0	0	None	0	0	8.99493E-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
S/A	0.2557	likely_benign	0.2413	benign	-0.579	Destabilizing	0.998	D	0.595	neutral	None	None	None	None	I
S/C	0.2245	likely_benign	0.1783	benign	-0.358	Destabilizing	1.0	D	0.751	deleterious	N	0.484717007	None	None	I
S/D	0.9159	likely_pathogenic	0.9298	pathogenic	-0.416	Destabilizing	0.999	D	0.751	deleterious	None	None	None	None	I
S/E	0.9424	likely_pathogenic	0.9511	pathogenic	-0.476	Destabilizing	0.999	D	0.72	prob.delet.	None	None	None	None	I
S/F	0.8499	likely_pathogenic	0.838	pathogenic	-1.022	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	I
S/G	0.3784	ambiguous	0.3383	benign	-0.754	Destabilizing	0.999	D	0.583	neutral	N	0.476414305	None	None	I
S/H	0.8385	likely_pathogenic	0.8145	pathogenic	-1.333	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	I
S/I	0.8965	likely_pathogenic	0.8819	pathogenic	-0.235	Destabilizing	1.0	D	0.802	deleterious	N	0.512251784	None	None	I
S/K	0.9869	likely_pathogenic	0.9851	pathogenic	-0.712	Destabilizing	0.999	D	0.738	prob.delet.	None	None	None	None	I
S/L	0.5108	ambiguous	0.5114	ambiguous	-0.235	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	I
S/M	0.649	likely_pathogenic	0.6475	pathogenic	0.23	Stabilizing	1.0	D	0.761	deleterious	None	None	None	None	I
S/N	0.5743	likely_pathogenic	0.4913	ambiguous	-0.539	Destabilizing	0.999	D	0.73	prob.delet.	N	0.500895478	None	None	I
S/P	0.9936	likely_pathogenic	0.9942	pathogenic	-0.319	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	I
S/Q	0.8981	likely_pathogenic	0.8803	pathogenic	-0.828	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	I
S/R	0.9775	likely_pathogenic	0.9704	pathogenic	-0.473	Destabilizing	1.0	D	0.767	deleterious	N	0.498867562	None	None	I
S/T	0.355	ambiguous	0.361	ambiguous	-0.58	Destabilizing	0.999	D	0.6	neutral	N	0.473321022	None	None	I
S/V	0.7902	likely_pathogenic	0.7717	pathogenic	-0.319	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	I
S/W	0.8881	likely_pathogenic	0.8844	pathogenic	-0.994	Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	I
S/Y	0.7817	likely_pathogenic	0.771	pathogenic	-0.733	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	I

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.