TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23249	69970;69971;69972	chr2:178576387;178576386;178576385	chr2:179441114;179441113;179441112
N2AB	21608	65047;65048;65049	chr2:178576387;178576386;178576385	chr2:179441114;179441113;179441112
N2A	20681	62266;62267;62268	chr2:178576387;178576386;178576385	chr2:179441114;179441113;179441112
N2B	14184	42775;42776;42777	chr2:178576387;178576386;178576385	chr2:179441114;179441113;179441112
Novex-1	14309	43150;43151;43152	chr2:178576387;178576386;178576385	chr2:179441114;179441113;179441112
Novex-2	14376	43351;43352;43353	chr2:178576387;178576386;178576385	chr2:179441114;179441113;179441112
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Fn3-57
• Domain position: 10
• Structural Position: 12
• Q(SASA): 0.4498
• 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
V/F	None	None	0.497	N	0.611	0.253	0.667787145914	gnomAD-4.0.0	1.72789E-06	None	None	None	None	I	None	0	3.19428E-05	None	0	0	None	0	0	0	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
V/A	0.5547	ambiguous	0.5577	ambiguous	-1.449	Destabilizing	0.001	N	0.273	neutral	N	0.521809895	None	None	I
V/C	0.836	likely_pathogenic	0.818	pathogenic	-1.065	Destabilizing	0.909	D	0.625	neutral	None	None	None	None	I
V/D	0.972	likely_pathogenic	0.9719	pathogenic	-1.016	Destabilizing	0.667	D	0.691	prob.neutral	N	0.515929222	None	None	I
V/E	0.934	likely_pathogenic	0.9349	pathogenic	-1.003	Destabilizing	0.567	D	0.637	neutral	None	None	None	None	I
V/F	0.526	ambiguous	0.5419	ambiguous	-1.148	Destabilizing	0.497	N	0.611	neutral	N	0.487083637	None	None	I
V/G	0.7916	likely_pathogenic	0.7917	pathogenic	-1.783	Destabilizing	0.124	N	0.668	neutral	N	0.514915264	None	None	I
V/H	0.9643	likely_pathogenic	0.963	pathogenic	-1.247	Destabilizing	0.968	D	0.704	prob.neutral	None	None	None	None	I
V/I	0.071	likely_benign	0.0735	benign	-0.632	Destabilizing	None	N	0.181	neutral	N	0.469671708	None	None	I
V/K	0.9139	likely_pathogenic	0.9119	pathogenic	-1.108	Destabilizing	0.567	D	0.639	neutral	None	None	None	None	I
V/L	0.331	likely_benign	0.349	ambiguous	-0.632	Destabilizing	0.009	N	0.449	neutral	N	0.519137737	None	None	I
V/M	0.3708	ambiguous	0.3612	ambiguous	-0.546	Destabilizing	0.567	D	0.58	neutral	None	None	None	None	I
V/N	0.9158	likely_pathogenic	0.9176	pathogenic	-0.923	Destabilizing	0.726	D	0.711	prob.delet.	None	None	None	None	I
V/P	0.8495	likely_pathogenic	0.8665	pathogenic	-0.869	Destabilizing	0.726	D	0.652	neutral	None	None	None	None	I
V/Q	0.9143	likely_pathogenic	0.9094	pathogenic	-1.048	Destabilizing	0.726	D	0.658	neutral	None	None	None	None	I
V/R	0.8887	likely_pathogenic	0.8898	pathogenic	-0.631	Destabilizing	0.726	D	0.712	prob.delet.	None	None	None	None	I
V/S	0.8175	likely_pathogenic	0.821	pathogenic	-1.499	Destabilizing	0.157	N	0.622	neutral	None	None	None	None	I
V/T	0.6873	likely_pathogenic	0.673	pathogenic	-1.355	Destabilizing	0.272	N	0.544	neutral	None	None	None	None	I
V/W	0.9755	likely_pathogenic	0.9728	pathogenic	-1.301	Destabilizing	0.968	D	0.716	prob.delet.	None	None	None	None	I
V/Y	0.9044	likely_pathogenic	0.9035	pathogenic	-1.006	Destabilizing	0.726	D	0.629	neutral	None	None	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.