TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31466	94621;94622;94623	chr2:178547129;178547128;178547127	chr2:179411856;179411855;179411854
N2AB	29825	89698;89699;89700	chr2:178547129;178547128;178547127	chr2:179411856;179411855;179411854
N2A	28898	86917;86918;86919	chr2:178547129;178547128;178547127	chr2:179411856;179411855;179411854
N2B	22401	67426;67427;67428	chr2:178547129;178547128;178547127	chr2:179411856;179411855;179411854
Novex-1	22526	67801;67802;67803	chr2:178547129;178547128;178547127	chr2:179411856;179411855;179411854
Novex-2	22593	68002;68003;68004	chr2:178547129;178547128;178547127	chr2:179411856;179411855;179411854
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGC
• RefSeq wild type template codon: ACG
• Domain: Fn3-117
• Domain position: 59
• Structural Position: 89
• Q(SASA): 0.1914
• Predicted PPI site: I

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
C/G	rs1697549166	None	1.0	N	0.779	0.501	0.816487136085	gnomAD-4.0.0	1.59128E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85847E-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
C/A	0.4054	ambiguous	0.3932	ambiguous	-2.123	Highly Destabilizing	0.998	D	0.561	neutral	None	None	None	None	I
C/D	0.7049	likely_pathogenic	0.7486	pathogenic	-1.261	Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	I
C/E	0.7694	likely_pathogenic	0.7945	pathogenic	-1.096	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	I
C/F	0.4238	ambiguous	0.462	ambiguous	-1.326	Destabilizing	1.0	D	0.795	deleterious	N	0.470956575	None	None	I
C/G	0.1423	likely_benign	0.1439	benign	-2.461	Highly Destabilizing	1.0	D	0.779	deleterious	N	0.459689175	None	None	I
C/H	0.5178	ambiguous	0.5746	pathogenic	-2.345	Highly Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	I
C/I	0.6913	likely_pathogenic	0.681	pathogenic	-1.213	Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	I
C/K	0.5307	ambiguous	0.5787	pathogenic	-1.648	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	I
C/L	0.4085	ambiguous	0.4027	ambiguous	-1.213	Destabilizing	0.999	D	0.559	neutral	None	None	None	None	I
C/M	0.573	likely_pathogenic	0.5682	pathogenic	0.162	Stabilizing	1.0	D	0.783	deleterious	None	None	None	None	I
C/N	0.3032	likely_benign	0.3283	benign	-1.892	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	I
C/P	0.6987	likely_pathogenic	0.6697	pathogenic	-1.494	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	I
C/Q	0.4727	ambiguous	0.4985	ambiguous	-1.645	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	I
C/R	0.2454	likely_benign	0.2934	benign	-1.535	Destabilizing	1.0	D	0.831	deleterious	N	0.446055769	None	None	I
C/S	0.3107	likely_benign	0.3285	benign	-2.374	Highly Destabilizing	1.0	D	0.722	prob.delet.	N	0.495695156	None	None	I
C/T	0.3179	likely_benign	0.291	benign	-2.034	Highly Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	I
C/V	0.5339	ambiguous	0.5063	ambiguous	-1.494	Destabilizing	0.999	D	0.632	neutral	None	None	None	None	I
C/W	0.6604	likely_pathogenic	0.706	pathogenic	-1.449	Destabilizing	1.0	D	0.803	deleterious	N	0.483326839	None	None	I
C/Y	0.3905	ambiguous	0.4544	ambiguous	-1.449	Destabilizing	1.0	D	0.812	deleterious	N	0.48256637	None	None	I

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.