TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	10131	30616;30617;30618	chr2:178702496;178702495;178702494	chr2:179567223;179567222;179567221
N2AB	9814	29665;29666;29667	chr2:178702496;178702495;178702494	chr2:179567223;179567222;179567221
N2A	8887	26884;26885;26886	chr2:178702496;178702495;178702494	chr2:179567223;179567222;179567221
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: C
• RefSeq wild type transcript codon: TGC
• RefSeq wild type template codon: ACG
• Domain: Ig-86
• Domain position: 54
• Structural Position: 135
• Q(SASA): 0.2587
• 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
C/W	rs913255032	None	0.006	None	0.415	0.259	0.465975295344	gnomAD-4.0.0	1.59087E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85745E-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	0.7798	likely_pathogenic	0.8302	pathogenic	-2.05	Highly Destabilizing	0.013	N	0.132	neutral	None	None	None	None	N
C/D	0.9528	likely_pathogenic	0.9664	pathogenic	-1.66	Destabilizing	0.828	D	0.589	neutral	None	None	None	None	N
C/E	0.9521	likely_pathogenic	0.968	pathogenic	-1.53	Destabilizing	0.704	D	0.535	neutral	None	None	None	None	N
C/F	0.4823	ambiguous	0.5388	ambiguous	-1.382	Destabilizing	0.759	D	0.554	neutral	None	None	None	None	N
C/G	0.6006	likely_pathogenic	0.6531	pathogenic	-2.356	Highly Destabilizing	0.425	N	0.491	neutral	None	None	None	None	N
C/H	0.6261	likely_pathogenic	0.7117	pathogenic	-2.486	Highly Destabilizing	0.981	D	0.559	neutral	None	None	None	None	N
C/I	0.7054	likely_pathogenic	0.7783	pathogenic	-1.239	Destabilizing	0.828	D	0.513	neutral	None	None	None	None	N
C/K	0.8202	likely_pathogenic	0.867	pathogenic	-1.857	Destabilizing	0.329	N	0.518	neutral	None	None	None	None	N
C/L	0.7117	likely_pathogenic	0.7481	pathogenic	-1.239	Destabilizing	0.495	N	0.431	neutral	None	None	None	None	N
C/M	0.8223	likely_pathogenic	0.8501	pathogenic	0.131	Stabilizing	0.981	D	0.512	neutral	None	None	None	None	N
C/N	0.7704	likely_pathogenic	0.8245	pathogenic	-1.966	Destabilizing	0.944	D	0.581	neutral	None	None	None	None	N
C/P	0.9976	likely_pathogenic	0.9981	pathogenic	-1.488	Destabilizing	0.944	D	0.575	neutral	None	None	None	None	N
C/Q	0.7431	likely_pathogenic	0.7925	pathogenic	-1.814	Destabilizing	0.893	D	0.575	neutral	None	None	None	None	N
C/R	0.4604	ambiguous	0.5288	ambiguous	-1.718	Destabilizing	0.002	N	0.363	neutral	None	None	None	None	N
C/S	0.6462	likely_pathogenic	0.7152	pathogenic	-2.368	Highly Destabilizing	0.27	N	0.459	neutral	None	None	None	None	N
C/T	0.6943	likely_pathogenic	0.7591	pathogenic	-2.088	Highly Destabilizing	0.704	D	0.491	neutral	None	None	None	None	N
C/V	0.608	likely_pathogenic	0.6875	pathogenic	-1.488	Destabilizing	0.704	D	0.488	neutral	None	None	None	None	N
C/W	0.699	likely_pathogenic	0.7571	pathogenic	-1.57	Destabilizing	0.006	N	0.415	neutral	None	None	None	None	N
C/Y	0.5408	ambiguous	0.6345	pathogenic	-1.539	Destabilizing	0.759	D	0.551	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.