TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9259	28000;28001;28002	chr2:178712055;178712054;178712053	chr2:179576782;179576781;179576780
N2AB	8942	27049;27050;27051	chr2:178712055;178712054;178712053	chr2:179576782;179576781;179576780
N2A	8015	24268;24269;24270	chr2:178712055;178712054;178712053	chr2:179576782;179576781;179576780
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: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-78
• Domain position: 55
• Structural Position: 135
• Q(SASA): 0.1745
• 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
V/I	rs2076736013	None	0.001	N	0.256	0.108	0.425148423609	gnomAD-4.0.0	6.36511E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.14334E-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
V/A	0.2312	likely_benign	0.3611	ambiguous	-1.692	Destabilizing	0.004	N	0.371	neutral	D	0.527842938	None	None	N
V/C	0.803	likely_pathogenic	0.8593	pathogenic	-1.128	Destabilizing	0.968	D	0.659	neutral	None	None	None	None	N
V/D	0.433	ambiguous	0.5805	pathogenic	-2.006	Highly Destabilizing	0.667	D	0.742	deleterious	N	0.495615877	None	None	N
V/E	0.3013	likely_benign	0.3735	ambiguous	-1.985	Destabilizing	0.726	D	0.696	prob.neutral	None	None	None	None	N
V/F	0.1984	likely_benign	0.2653	benign	-1.342	Destabilizing	0.497	N	0.697	prob.neutral	N	0.496252621	None	None	N
V/G	0.418	ambiguous	0.5747	pathogenic	-2.037	Highly Destabilizing	0.497	N	0.681	prob.neutral	N	0.463082171	None	None	N
V/H	0.6155	likely_pathogenic	0.7145	pathogenic	-1.676	Destabilizing	0.968	D	0.711	prob.delet.	None	None	None	None	N
V/I	0.0663	likely_benign	0.0698	benign	-0.82	Destabilizing	0.001	N	0.256	neutral	N	0.478030194	None	None	N
V/K	0.408	ambiguous	0.503	ambiguous	-1.36	Destabilizing	0.726	D	0.697	prob.neutral	None	None	None	None	N
V/L	0.2481	likely_benign	0.3179	benign	-0.82	Destabilizing	0.02	N	0.481	neutral	N	0.505467511	None	None	N
V/M	0.1289	likely_benign	0.1687	benign	-0.593	Destabilizing	0.567	D	0.596	neutral	None	None	None	None	N
V/N	0.3312	likely_benign	0.4456	ambiguous	-1.212	Destabilizing	0.89	D	0.741	deleterious	None	None	None	None	N
V/P	0.9735	likely_pathogenic	0.9899	pathogenic	-1.078	Destabilizing	0.726	D	0.707	prob.neutral	None	None	None	None	N
V/Q	0.3796	ambiguous	0.4603	ambiguous	-1.386	Destabilizing	0.89	D	0.705	prob.neutral	None	None	None	None	N
V/R	0.38	ambiguous	0.4691	ambiguous	-0.861	Destabilizing	0.726	D	0.741	deleterious	None	None	None	None	N
V/S	0.2908	likely_benign	0.3956	ambiguous	-1.696	Destabilizing	0.396	N	0.655	neutral	None	None	None	None	N
V/T	0.1494	likely_benign	0.1951	benign	-1.573	Destabilizing	0.272	N	0.579	neutral	None	None	None	None	N
V/W	0.8309	likely_pathogenic	0.9037	pathogenic	-1.618	Destabilizing	0.968	D	0.681	prob.neutral	None	None	None	None	N
V/Y	0.5728	likely_pathogenic	0.6504	pathogenic	-1.314	Destabilizing	0.726	D	0.7	prob.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.