TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7138	21637;21638;21639	chr2:178723688;178723687;178723686	chr2:179588415;179588414;179588413
N2AB	6821	20686;20687;20688	chr2:178723688;178723687;178723686	chr2:179588415;179588414;179588413
N2A	5894	17905;17906;17907	chr2:178723688;178723687;178723686	chr2:179588415;179588414;179588413
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-56
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.2617
• 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/A	rs2078830864	None	0.953	N	0.337	0.213	0.376039117802	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
S/A	rs2078830864	None	0.953	N	0.337	0.213	0.376039117802	gnomAD-4.0.0	6.57289E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47042E-05	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	0.0905	likely_benign	0.0892	benign	-0.369	Destabilizing	0.953	D	0.337	neutral	N	0.492694222	None	None	N
S/C	0.1474	likely_benign	0.1466	benign	-0.31	Destabilizing	0.265	N	0.332	neutral	N	0.517852823	None	None	N
S/D	0.536	ambiguous	0.5075	ambiguous	0.594	Stabilizing	0.993	D	0.481	neutral	None	None	None	None	N
S/E	0.5764	likely_pathogenic	0.5328	ambiguous	0.618	Stabilizing	0.999	D	0.486	neutral	None	None	None	None	N
S/F	0.1642	likely_benign	0.1479	benign	-0.681	Destabilizing	0.999	D	0.704	prob.neutral	N	0.502457593	None	None	N
S/G	0.1541	likely_benign	0.1585	benign	-0.601	Destabilizing	0.171	N	0.179	neutral	None	None	None	None	N
S/H	0.3867	ambiguous	0.3477	ambiguous	-0.89	Destabilizing	1.0	D	0.583	neutral	None	None	None	None	N
S/I	0.1753	likely_benign	0.1609	benign	0.138	Stabilizing	0.998	D	0.693	prob.neutral	None	None	None	None	N
S/K	0.7171	likely_pathogenic	0.6749	pathogenic	-0.035	Destabilizing	0.993	D	0.485	neutral	None	None	None	None	N
S/L	0.1026	likely_benign	0.1018	benign	0.138	Stabilizing	0.985	D	0.586	neutral	None	None	None	None	N
S/M	0.2649	likely_benign	0.2515	benign	-0.057	Destabilizing	1.0	D	0.584	neutral	None	None	None	None	N
S/N	0.2613	likely_benign	0.2467	benign	-0.144	Destabilizing	0.993	D	0.501	neutral	None	None	None	None	N
S/P	0.8973	likely_pathogenic	0.8946	pathogenic	0.003	Stabilizing	0.999	D	0.598	neutral	N	0.5219542	None	None	N
S/Q	0.5533	ambiguous	0.5128	ambiguous	-0.132	Destabilizing	0.999	D	0.519	neutral	None	None	None	None	N
S/R	0.5601	ambiguous	0.5143	ambiguous	-0.08	Destabilizing	0.999	D	0.598	neutral	None	None	None	None	N
S/T	0.0946	likely_benign	0.0936	benign	-0.165	Destabilizing	0.99	D	0.497	neutral	D	0.534270265	None	None	N
S/V	0.1615	likely_benign	0.1502	benign	0.003	Stabilizing	0.996	D	0.61	neutral	None	None	None	None	N
S/W	0.3741	ambiguous	0.345	ambiguous	-0.753	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
S/Y	0.1781	likely_benign	0.157	benign	-0.379	Destabilizing	0.999	D	0.699	prob.neutral	N	0.486150537	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.