TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27868	83827;83828;83829	chr2:178562530;178562529;178562528	chr2:179427257;179427256;179427255
N2AB	26227	78904;78905;78906	chr2:178562530;178562529;178562528	chr2:179427257;179427256;179427255
N2A	25300	76123;76124;76125	chr2:178562530;178562529;178562528	chr2:179427257;179427256;179427255
N2B	18803	56632;56633;56634	chr2:178562530;178562529;178562528	chr2:179427257;179427256;179427255
Novex-1	18928	57007;57008;57009	chr2:178562530;178562529;178562528	chr2:179427257;179427256;179427255
Novex-2	18995	57208;57209;57210	chr2:178562530;178562529;178562528	chr2:179427257;179427256;179427255
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Fn3-91
• Domain position: 6
• Structural Position: 6
• Q(SASA): 0.1547
• 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
G/R	None	None	0.999	D	0.863	0.291	0.474722520063	gnomAD-4.0.0	6.85767E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00328E-07	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
G/A	0.1822	likely_benign	0.2022	benign	-0.875	Destabilizing	0.228	N	0.431	neutral	N	0.483307748	None	None	N
G/C	0.3499	ambiguous	0.3934	ambiguous	-1.011	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
G/D	0.6107	likely_pathogenic	0.6881	pathogenic	-2.064	Highly Destabilizing	0.999	D	0.823	deleterious	None	None	None	None	N
G/E	0.4498	ambiguous	0.5379	ambiguous	-2.052	Highly Destabilizing	0.999	D	0.835	deleterious	N	0.518209443	None	None	N
G/F	0.7734	likely_pathogenic	0.8104	pathogenic	-0.996	Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
G/H	0.6696	likely_pathogenic	0.7335	pathogenic	-1.759	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
G/I	0.5307	ambiguous	0.5806	pathogenic	-0.289	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
G/K	0.6406	likely_pathogenic	0.7183	pathogenic	-1.651	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
G/L	0.547	ambiguous	0.6088	pathogenic	-0.289	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
G/M	0.6392	likely_pathogenic	0.6818	pathogenic	-0.247	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
G/N	0.5348	ambiguous	0.5844	pathogenic	-1.449	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
G/P	0.9423	likely_pathogenic	0.957	pathogenic	-0.443	Destabilizing	0.999	D	0.856	deleterious	None	None	None	None	N
G/Q	0.4887	ambiguous	0.5565	ambiguous	-1.547	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
G/R	0.4862	ambiguous	0.5698	pathogenic	-1.364	Destabilizing	0.999	D	0.863	deleterious	D	0.522423184	None	None	N
G/S	0.1446	likely_benign	0.154	benign	-1.636	Destabilizing	0.795	D	0.433	neutral	None	None	None	None	N
G/T	0.3141	likely_benign	0.3463	ambiguous	-1.557	Destabilizing	0.999	D	0.783	deleterious	None	None	None	None	N
G/V	0.3661	ambiguous	0.4109	ambiguous	-0.443	Destabilizing	0.999	D	0.815	deleterious	N	0.484321706	None	None	N
G/W	0.7178	likely_pathogenic	0.77	pathogenic	-1.562	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
G/Y	0.6898	likely_pathogenic	0.7384	pathogenic	-1.112	Destabilizing	1.0	D	0.857	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.