TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8034	24325;24326;24327	chr2:178719290;178719289;178719288	chr2:179584017;179584016;179584015
N2AB	7717	23374;23375;23376	chr2:178719290;178719289;178719288	chr2:179584017;179584016;179584015
N2A	6790	20593;20594;20595	chr2:178719290;178719289;178719288	chr2:179584017;179584016;179584015
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-65
• Domain position: 50
• Structural Position: 125
• Q(SASA): 0.4401
• 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/T	None	None	None	N	0.093	0.151	0.163833314356	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
S/A	0.0814	likely_benign	0.0824	benign	-0.683	Destabilizing	None	N	0.11	neutral	None	None	None	None	N
S/C	0.1142	likely_benign	0.1145	benign	-0.379	Destabilizing	0.851	D	0.359	neutral	D	0.527336251	None	None	N
S/D	0.2297	likely_benign	0.2628	benign	0.223	Stabilizing	0.22	N	0.223	neutral	None	None	None	None	N
S/E	0.3275	likely_benign	0.3688	ambiguous	0.168	Stabilizing	0.055	N	0.239	neutral	None	None	None	None	N
S/F	0.1352	likely_benign	0.1283	benign	-1.154	Destabilizing	0.497	N	0.439	neutral	None	None	None	None	N
S/G	0.082	likely_benign	0.0968	benign	-0.853	Destabilizing	0.042	N	0.232	neutral	N	0.501888162	None	None	N
S/H	0.1815	likely_benign	0.1971	benign	-1.352	Destabilizing	0.667	D	0.377	neutral	None	None	None	None	N
S/I	0.1037	likely_benign	0.1065	benign	-0.355	Destabilizing	0.096	N	0.413	neutral	D	0.531520749	None	None	N
S/K	0.3699	ambiguous	0.4024	ambiguous	-0.504	Destabilizing	0.001	N	0.106	neutral	None	None	None	None	N
S/L	0.0931	likely_benign	0.0909	benign	-0.355	Destabilizing	0.001	N	0.268	neutral	None	None	None	None	N
S/M	0.1725	likely_benign	0.1811	benign	-0.052	Destabilizing	0.497	N	0.391	neutral	None	None	None	None	N
S/N	0.1012	likely_benign	0.109	benign	-0.324	Destabilizing	0.175	N	0.253	neutral	N	0.488783883	None	None	N
S/P	0.5288	ambiguous	0.5545	ambiguous	-0.434	Destabilizing	0.364	N	0.412	neutral	None	None	None	None	N
S/Q	0.3022	likely_benign	0.3362	benign	-0.518	Destabilizing	0.124	N	0.304	neutral	None	None	None	None	N
S/R	0.2798	likely_benign	0.2988	benign	-0.368	Destabilizing	None	N	0.153	neutral	D	0.526362858	None	None	N
S/T	0.0696	likely_benign	0.0697	benign	-0.425	Destabilizing	None	N	0.093	neutral	N	0.448478078	None	None	N
S/V	0.1158	likely_benign	0.1193	benign	-0.434	Destabilizing	0.055	N	0.395	neutral	None	None	None	None	N
S/W	0.2404	likely_benign	0.2451	benign	-1.109	Destabilizing	0.958	D	0.45	neutral	None	None	None	None	N
S/Y	0.1283	likely_benign	0.1245	benign	-0.845	Destabilizing	0.859	D	0.442	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.