TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6130	18613;18614;18615	chr2:178729865;178729864;178729863	chr2:179594592;179594591;179594590
N2AB	5813	17662;17663;17664	chr2:178729865;178729864;178729863	chr2:179594592;179594591;179594590
N2A	4886	14881;14882;14883	chr2:178729865;178729864;178729863	chr2:179594592;179594591;179594590
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: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-45
• Domain position: 26
• Structural Position: 38
• Q(SASA): 0.4894
• 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
T/R	rs1379804888	None	0.942	N	0.582	0.346	0.754986483899	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
T/R	rs1379804888	None	0.942	N	0.582	0.346	0.754986483899	gnomAD-4.0.0	8.96994E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.67537E-05	0	0
T/S	rs794727816	None	0.698	N	0.391	0.218	0.218845423259	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-06	0	3.66327E-05

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
T/A	0.0687	likely_benign	0.0697	benign	-0.58	Destabilizing	0.014	N	0.223	neutral	N	0.499061614	None	None	N
T/C	0.4262	ambiguous	0.4435	ambiguous	-0.41	Destabilizing	0.994	D	0.553	neutral	None	None	None	None	N
T/D	0.3241	likely_benign	0.3451	ambiguous	0.222	Stabilizing	0.978	D	0.558	neutral	None	None	None	None	N
T/E	0.231	likely_benign	0.2427	benign	0.227	Stabilizing	0.956	D	0.518	neutral	None	None	None	None	N
T/F	0.1894	likely_benign	0.2054	benign	-0.714	Destabilizing	0.978	D	0.64	neutral	None	None	None	None	N
T/G	0.2118	likely_benign	0.2243	benign	-0.828	Destabilizing	0.754	D	0.518	neutral	None	None	None	None	N
T/H	0.2039	likely_benign	0.2166	benign	-1.056	Destabilizing	0.998	D	0.615	neutral	None	None	None	None	N
T/I	0.1338	likely_benign	0.1374	benign	-0.02	Destabilizing	0.698	D	0.493	neutral	D	0.531366033	None	None	N
T/K	0.1366	likely_benign	0.1398	benign	-0.498	Destabilizing	0.942	D	0.524	neutral	N	0.516049864	None	None	N
T/L	0.0938	likely_benign	0.0984	benign	-0.02	Destabilizing	0.754	D	0.398	neutral	None	None	None	None	N
T/M	0.0939	likely_benign	0.0949	benign	0.008	Stabilizing	0.994	D	0.564	neutral	None	None	None	None	N
T/N	0.1151	likely_benign	0.1198	benign	-0.453	Destabilizing	0.978	D	0.524	neutral	None	None	None	None	N
T/P	0.3319	likely_benign	0.3966	ambiguous	-0.174	Destabilizing	0.971	D	0.578	neutral	N	0.516878545	None	None	N
T/Q	0.185	likely_benign	0.1887	benign	-0.526	Destabilizing	0.978	D	0.58	neutral	None	None	None	None	N
T/R	0.1025	likely_benign	0.1064	benign	-0.351	Destabilizing	0.942	D	0.582	neutral	N	0.52078368	None	None	N
T/S	0.0887	likely_benign	0.0924	benign	-0.735	Destabilizing	0.698	D	0.391	neutral	N	0.446131206	None	None	N
T/V	0.1241	likely_benign	0.1237	benign	-0.174	Destabilizing	0.019	N	0.303	neutral	None	None	None	None	N
T/W	0.4736	ambiguous	0.5144	ambiguous	-0.709	Destabilizing	0.998	D	0.641	neutral	None	None	None	None	N
T/Y	0.2305	likely_benign	0.2583	benign	-0.435	Destabilizing	0.993	D	0.634	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.