TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29385	88378;88379;88380	chr2:178557001;178557000;178556999	chr2:179421728;179421727;179421726
N2AB	27744	83455;83456;83457	chr2:178557001;178557000;178556999	chr2:179421728;179421727;179421726
N2A	26817	80674;80675;80676	chr2:178557001;178557000;178556999	chr2:179421728;179421727;179421726
N2B	20320	61183;61184;61185	chr2:178557001;178557000;178556999	chr2:179421728;179421727;179421726
Novex-1	20445	61558;61559;61560	chr2:178557001;178557000;178556999	chr2:179421728;179421727;179421726
Novex-2	20512	61759;61760;61761	chr2:178557001;178557000;178556999	chr2:179421728;179421727;179421726
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: Fn3-102
• Domain position: 51
• Structural Position: 68
• Q(SASA): 0.2864
• 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
A/T	None	None	0.884	N	0.383	0.205	0.194818534648	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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
A/C	0.5458	ambiguous	0.5448	ambiguous	-0.401	Destabilizing	1.0	D	0.766	deleterious	None	None	None	None	I
A/D	0.8707	likely_pathogenic	0.8536	pathogenic	-0.225	Destabilizing	0.999	D	0.768	deleterious	N	0.480010886	None	None	I
A/E	0.822	likely_pathogenic	0.8152	pathogenic	-0.109	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	I
A/F	0.7394	likely_pathogenic	0.692	pathogenic	-0.268	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	I
A/G	0.2142	likely_benign	0.1811	benign	-0.785	Destabilizing	0.998	D	0.53	neutral	N	0.480264376	None	None	I
A/H	0.9128	likely_pathogenic	0.9177	pathogenic	-1.078	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	I
A/I	0.5189	ambiguous	0.47	ambiguous	0.607	Stabilizing	0.999	D	0.786	deleterious	None	None	None	None	I
A/K	0.9622	likely_pathogenic	0.9632	pathogenic	-0.373	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	I
A/L	0.4846	ambiguous	0.4519	ambiguous	0.607	Stabilizing	0.997	D	0.618	neutral	None	None	None	None	I
A/M	0.5345	ambiguous	0.5084	ambiguous	0.331	Stabilizing	1.0	D	0.809	deleterious	None	None	None	None	I
A/N	0.7536	likely_pathogenic	0.7462	pathogenic	-0.407	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	I
A/P	0.9202	likely_pathogenic	0.9154	pathogenic	0.323	Stabilizing	1.0	D	0.792	deleterious	N	0.488658167	None	None	I
A/Q	0.8518	likely_pathogenic	0.8603	pathogenic	-0.257	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	I
A/R	0.9385	likely_pathogenic	0.9404	pathogenic	-0.551	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	I
A/S	0.1757	likely_benign	0.1712	benign	-0.946	Destabilizing	0.992	D	0.503	neutral	N	0.466501761	None	None	I
A/T	0.1905	likely_benign	0.1829	benign	-0.685	Destabilizing	0.884	D	0.383	neutral	N	0.458437138	None	None	I
A/V	0.2293	likely_benign	0.2015	benign	0.323	Stabilizing	0.996	D	0.549	neutral	N	0.460435284	None	None	I
A/W	0.9713	likely_pathogenic	0.9685	pathogenic	-0.837	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	I
A/Y	0.8471	likely_pathogenic	0.8369	pathogenic	-0.23	Destabilizing	1.0	D	0.819	deleterious	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.