TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5278	16057;16058;16059	chr2:178733461;178733460;178733459	chr2:179598188;179598187;179598186
N2AB	4961	15106;15107;15108	chr2:178733461;178733460;178733459	chr2:179598188;179598187;179598186
N2A	4034	12325;12326;12327	chr2:178733461;178733460;178733459	chr2:179598188;179598187;179598186
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: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Ig-36
• Domain position: 18
• Structural Position: 28
• Q(SASA): 0.3941
• 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
A/T	rs754692422	-0.642	1.0	N	0.751	0.298	None	gnomAD-2.1.1	4.03E-05	None	None	None	None	N	None	0	1.45096E-04	None	0	0	None	9.81E-05	None	0	1.78E-05	0
A/T	rs754692422	-0.642	1.0	N	0.751	0.298	None	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	2.94E-05	0	0
A/T	rs754692422	-0.642	1.0	N	0.751	0.298	None	gnomAD-4.0.0	1.73522E-05	None	None	None	None	N	None	2.66973E-05	1.16678E-04	None	0	2.22866E-05	None	0	0	8.47642E-06	8.78426E-05	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
A/C	0.5895	likely_pathogenic	0.5874	pathogenic	-0.783	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	N
A/D	0.9533	likely_pathogenic	0.9121	pathogenic	-0.971	Destabilizing	1.0	D	0.801	deleterious	D	0.599432047	None	None	N
A/E	0.9034	likely_pathogenic	0.8261	pathogenic	-0.821	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
A/F	0.7195	likely_pathogenic	0.7049	pathogenic	-0.481	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
A/G	0.3187	likely_benign	0.3164	benign	-1.149	Destabilizing	1.0	D	0.62	neutral	D	0.53482684	None	None	N
A/H	0.9417	likely_pathogenic	0.9153	pathogenic	-1.421	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
A/I	0.3946	ambiguous	0.3643	ambiguous	0.438	Stabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
A/K	0.9596	likely_pathogenic	0.914	pathogenic	-0.787	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
A/L	0.4366	ambiguous	0.4138	ambiguous	0.438	Stabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
A/M	0.4698	ambiguous	0.4355	ambiguous	0.152	Stabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
A/N	0.8772	likely_pathogenic	0.8265	pathogenic	-0.877	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
A/P	0.9733	likely_pathogenic	0.9724	pathogenic	0.103	Stabilizing	1.0	D	0.801	deleterious	D	0.558319616	None	None	N
A/Q	0.866	likely_pathogenic	0.8015	pathogenic	-0.713	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
A/R	0.9264	likely_pathogenic	0.8638	pathogenic	-0.922	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
A/S	0.1957	likely_benign	0.1886	benign	-1.4	Destabilizing	1.0	D	0.635	neutral	D	0.544319676	None	None	N
A/T	0.1754	likely_benign	0.141	benign	-1.095	Destabilizing	1.0	D	0.751	deleterious	N	0.475766692	None	None	N
A/V	0.1653	likely_benign	0.1487	benign	0.103	Stabilizing	1.0	D	0.702	prob.neutral	N	0.412092184	None	None	N
A/W	0.9763	likely_pathogenic	0.9696	pathogenic	-1.06	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
A/Y	0.9087	likely_pathogenic	0.8795	pathogenic	-0.477	Destabilizing	1.0	D	0.816	deleterious	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.