TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18613	56062;56063;56064	chr2:178601067;178601066;178601065	chr2:179465794;179465793;179465792
N2AB	16972	51139;51140;51141	chr2:178601067;178601066;178601065	chr2:179465794;179465793;179465792
N2A	16045	48358;48359;48360	chr2:178601067;178601066;178601065	chr2:179465794;179465793;179465792
N2B	9548	28867;28868;28869	chr2:178601067;178601066;178601065	chr2:179465794;179465793;179465792
Novex-1	9673	29242;29243;29244	chr2:178601067;178601066;178601065	chr2:179465794;179465793;179465792
Novex-2	9740	29443;29444;29445	chr2:178601067;178601066;178601065	chr2:179465794;179465793;179465792
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAC
• RefSeq wild type template codon: GTG
• Domain: Fn3-23
• Domain position: 35
• Structural Position: 37
• Q(SASA): 0.1247
• 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
H/D	None	None	1.0	N	0.691	0.497	0.376039117802	gnomAD-4.0.0	1.59674E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43968E-05	0
H/P	None	None	1.0	N	0.798	0.654	0.628066502817	gnomAD-4.0.0	1.59553E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86554E-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
H/A	0.7351	likely_pathogenic	0.7597	pathogenic	-1.246	Destabilizing	0.999	D	0.629	neutral	None	None	None	None	N
H/C	0.3757	ambiguous	0.4056	ambiguous	-0.398	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
H/D	0.723	likely_pathogenic	0.7464	pathogenic	-1.018	Destabilizing	1.0	D	0.691	prob.neutral	N	0.497084809	None	None	N
H/E	0.852	likely_pathogenic	0.8541	pathogenic	-0.875	Destabilizing	0.999	D	0.485	neutral	None	None	None	None	N
H/F	0.763	likely_pathogenic	0.7759	pathogenic	0.309	Stabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
H/G	0.4853	ambiguous	0.5497	ambiguous	-1.627	Destabilizing	0.999	D	0.667	neutral	None	None	None	None	N
H/I	0.97	likely_pathogenic	0.97	pathogenic	-0.157	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
H/K	0.6778	likely_pathogenic	0.7202	pathogenic	-0.887	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
H/L	0.7053	likely_pathogenic	0.6919	pathogenic	-0.157	Destabilizing	1.0	D	0.779	deleterious	N	0.520673745	None	None	N
H/M	0.9309	likely_pathogenic	0.9312	pathogenic	-0.313	Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	N
H/N	0.3326	likely_benign	0.3443	ambiguous	-1.19	Destabilizing	0.999	D	0.497	neutral	N	0.461105366	None	None	N
H/P	0.9677	likely_pathogenic	0.974	pathogenic	-0.504	Destabilizing	1.0	D	0.798	deleterious	N	0.493018212	None	None	N
H/Q	0.6538	likely_pathogenic	0.6472	pathogenic	-0.865	Destabilizing	1.0	D	0.685	prob.neutral	N	0.509109957	None	None	N
H/R	0.3387	likely_benign	0.3467	ambiguous	-1.192	Destabilizing	1.0	D	0.647	neutral	N	0.47672818	None	None	N
H/S	0.4991	ambiguous	0.5371	ambiguous	-1.27	Destabilizing	1.0	D	0.69	prob.neutral	None	None	None	None	N
H/T	0.8201	likely_pathogenic	0.8364	pathogenic	-1.027	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
H/V	0.931	likely_pathogenic	0.9314	pathogenic	-0.504	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
H/W	0.8039	likely_pathogenic	0.8232	pathogenic	0.718	Stabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
H/Y	0.3192	likely_benign	0.3276	benign	0.699	Stabilizing	0.999	D	0.539	neutral	N	0.497431526	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.