TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9056	27391;27392;27393	chr2:178712859;178712858;178712857	chr2:179577586;179577585;179577584
N2AB	8739	26440;26441;26442	chr2:178712859;178712858;178712857	chr2:179577586;179577585;179577584
N2A	7812	23659;23660;23661	chr2:178712859;178712858;178712857	chr2:179577586;179577585;179577584
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: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Ig-76
• Domain position: 38
• Structural Position: 52
• Q(SASA): 0.8274
• 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
S/N	None	None	0.002	N	0.148	0.083	0.0716867268079	gnomAD-4.0.0	6.84251E-07	None	None	None	None	N	None	0	0	None	0	2.52042E-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
S/A	0.0831	likely_benign	0.0849	benign	-0.264	Destabilizing	0.004	N	0.125	neutral	None	None	None	None	N
S/C	0.1876	likely_benign	0.1908	benign	-0.534	Destabilizing	0.978	D	0.326	neutral	N	0.452996316	None	None	N
S/D	0.2351	likely_benign	0.305	benign	0.07	Stabilizing	0.129	N	0.235	neutral	None	None	None	None	N
S/E	0.3448	ambiguous	0.4341	ambiguous	-0.03	Destabilizing	0.01	N	0.145	neutral	None	None	None	None	N
S/F	0.1633	likely_benign	0.1744	benign	-1.054	Destabilizing	0.94	D	0.349	neutral	None	None	None	None	N
S/G	0.0916	likely_benign	0.0974	benign	-0.277	Destabilizing	None	N	0.115	neutral	N	0.380123487	None	None	N
S/H	0.2825	likely_benign	0.3342	benign	-0.501	Destabilizing	0.716	D	0.321	neutral	None	None	None	None	N
S/I	0.1551	likely_benign	0.1656	benign	-0.354	Destabilizing	0.794	D	0.386	neutral	N	0.476127	None	None	N
S/K	0.4582	ambiguous	0.57	pathogenic	-0.37	Destabilizing	0.129	N	0.232	neutral	None	None	None	None	N
S/L	0.1027	likely_benign	0.1056	benign	-0.354	Destabilizing	0.418	N	0.349	neutral	None	None	None	None	N
S/M	0.205	likely_benign	0.2161	benign	-0.395	Destabilizing	0.94	D	0.324	neutral	None	None	None	None	N
S/N	0.1045	likely_benign	0.1213	benign	-0.231	Destabilizing	0.002	N	0.148	neutral	N	0.411089473	None	None	N
S/P	0.1227	likely_benign	0.1397	benign	-0.303	Destabilizing	0.593	D	0.411	neutral	None	None	None	None	N
S/Q	0.3636	ambiguous	0.4373	ambiguous	-0.392	Destabilizing	0.027	N	0.183	neutral	None	None	None	None	N
S/R	0.383	ambiguous	0.4773	ambiguous	-0.148	Destabilizing	0.351	N	0.391	neutral	N	0.451728868	None	None	N
S/T	0.0909	likely_benign	0.0947	benign	-0.347	Destabilizing	0.183	N	0.265	neutral	N	0.488704894	None	None	N
S/V	0.1751	likely_benign	0.1815	benign	-0.303	Destabilizing	0.418	N	0.355	neutral	None	None	None	None	N
S/W	0.2784	likely_benign	0.32	benign	-1.154	Destabilizing	0.983	D	0.379	neutral	None	None	None	None	N
S/Y	0.1585	likely_benign	0.1754	benign	-0.835	Destabilizing	0.94	D	0.351	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.