TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6138	18637;18638;18639	chr2:178729841;178729840;178729839	chr2:179594568;179594567;179594566
N2AB	5821	17686;17687;17688	chr2:178729841;178729840;178729839	chr2:179594568;179594567;179594566
N2A	4894	14905;14906;14907	chr2:178729841;178729840;178729839	chr2:179594568;179594567;179594566
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: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-45
• Domain position: 34
• Structural Position: 47
• Q(SASA): 0.1511
• 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/F	None	None	0.473	N	0.585	0.391	0.517765160837	gnomAD-4.0.0	6.84262E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15934E-05	0
S/Y	rs727504477	-0.123	0.01	N	0.417	0.336	0.468420198123	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
S/Y	rs727504477	-0.123	0.01	N	0.417	0.336	0.468420198123	gnomAD-4.0.0	7.52688E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.89447E-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	0.0851	likely_benign	0.0846	benign	-0.64	Destabilizing	0.002	N	0.193	neutral	N	0.496813529	None	None	N
S/C	0.1551	likely_benign	0.171	benign	-0.306	Destabilizing	0.927	D	0.585	neutral	D	0.526021715	None	None	N
S/D	0.3308	likely_benign	0.3298	benign	-0.351	Destabilizing	0.329	N	0.448	neutral	None	None	None	None	N
S/E	0.4547	ambiguous	0.4482	ambiguous	-0.286	Destabilizing	0.495	N	0.437	neutral	None	None	None	None	N
S/F	0.1578	likely_benign	0.1605	benign	-0.566	Destabilizing	0.473	N	0.585	neutral	N	0.510764261	None	None	N
S/G	0.1133	likely_benign	0.1177	benign	-0.962	Destabilizing	0.329	N	0.43	neutral	None	None	None	None	N
S/H	0.2655	likely_benign	0.2654	benign	-1.355	Destabilizing	0.893	D	0.593	neutral	None	None	None	None	N
S/I	0.1519	likely_benign	0.1494	benign	0.13	Stabilizing	0.704	D	0.58	neutral	None	None	None	None	N
S/K	0.5015	ambiguous	0.4868	ambiguous	-0.58	Destabilizing	0.495	N	0.439	neutral	None	None	None	None	N
S/L	0.1042	likely_benign	0.1045	benign	0.13	Stabilizing	0.329	N	0.545	neutral	None	None	None	None	N
S/M	0.2136	likely_benign	0.2121	benign	0.217	Stabilizing	0.981	D	0.583	neutral	None	None	None	None	N
S/N	0.1198	likely_benign	0.1227	benign	-0.69	Destabilizing	0.013	N	0.22	neutral	None	None	None	None	N
S/P	0.8175	likely_pathogenic	0.7956	pathogenic	-0.091	Destabilizing	0.784	D	0.593	neutral	N	0.51360377	None	None	N
S/Q	0.4116	ambiguous	0.4114	ambiguous	-0.665	Destabilizing	0.828	D	0.547	neutral	None	None	None	None	N
S/R	0.3673	ambiguous	0.3711	ambiguous	-0.631	Destabilizing	0.704	D	0.577	neutral	None	None	None	None	N
S/T	0.0783	likely_benign	0.0783	benign	-0.601	Destabilizing	0.003	N	0.181	neutral	N	0.395745245	None	None	N
S/V	0.174	likely_benign	0.174	benign	-0.091	Destabilizing	0.329	N	0.549	neutral	None	None	None	None	N
S/W	0.2738	likely_benign	0.2785	benign	-0.665	Destabilizing	0.985	D	0.617	neutral	None	None	None	None	N
S/Y	0.16	likely_benign	0.1604	benign	-0.347	Destabilizing	0.01	N	0.417	neutral	N	0.475747611	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.