TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29323	88192;88193;88194	chr2:178557295;178557294;178557293	chr2:179422022;179422021;179422020
N2AB	27682	83269;83270;83271	chr2:178557295;178557294;178557293	chr2:179422022;179422021;179422020
N2A	26755	80488;80489;80490	chr2:178557295;178557294;178557293	chr2:179422022;179422021;179422020
N2B	20258	60997;60998;60999	chr2:178557295;178557294;178557293	chr2:179422022;179422021;179422020
Novex-1	20383	61372;61373;61374	chr2:178557295;178557294;178557293	chr2:179422022;179422021;179422020
Novex-2	20450	61573;61574;61575	chr2:178557295;178557294;178557293	chr2:179422022;179422021;179422020
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-101
• Domain position: 87
• Structural Position: 120
• Q(SASA): 0.1913
• 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
P/S	rs1371741615	-1.452	0.012	N	0.396	0.141	0.200317383148	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
P/S	rs1371741615	-1.452	0.012	N	0.396	0.141	0.200317383148	gnomAD-4.0.0	1.59113E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85768E-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
P/A	0.0727	likely_benign	0.0681	benign	-1.69	Destabilizing	None	N	0.263	neutral	N	0.478170975	None	None	I
P/C	0.4443	ambiguous	0.4101	ambiguous	-0.836	Destabilizing	0.356	N	0.562	neutral	None	None	None	None	I
P/D	0.9246	likely_pathogenic	0.9096	pathogenic	-1.627	Destabilizing	0.136	N	0.511	neutral	None	None	None	None	I
P/E	0.7548	likely_pathogenic	0.7101	pathogenic	-1.585	Destabilizing	0.072	N	0.475	neutral	None	None	None	None	I
P/F	0.7008	likely_pathogenic	0.6744	pathogenic	-1.224	Destabilizing	None	N	0.463	neutral	None	None	None	None	I
P/G	0.4883	ambiguous	0.419	ambiguous	-2.047	Highly Destabilizing	0.016	N	0.434	neutral	None	None	None	None	I
P/H	0.603	likely_pathogenic	0.5838	pathogenic	-1.651	Destabilizing	0.56	D	0.547	neutral	N	0.495549426	None	None	I
P/I	0.5235	ambiguous	0.4618	ambiguous	-0.781	Destabilizing	None	N	0.46	neutral	None	None	None	None	I
P/K	0.7904	likely_pathogenic	0.7599	pathogenic	-1.347	Destabilizing	0.072	N	0.477	neutral	None	None	None	None	I
P/L	0.3189	likely_benign	0.2968	benign	-0.781	Destabilizing	None	N	0.452	neutral	N	0.493014531	None	None	I
P/M	0.4628	ambiguous	0.46	ambiguous	-0.486	Destabilizing	0.12	N	0.595	neutral	None	None	None	None	I
P/N	0.7856	likely_pathogenic	0.7545	pathogenic	-1.148	Destabilizing	0.136	N	0.616	neutral	None	None	None	None	I
P/Q	0.503	ambiguous	0.4573	ambiguous	-1.274	Destabilizing	0.356	N	0.535	neutral	None	None	None	None	I
P/R	0.6685	likely_pathogenic	0.6353	pathogenic	-0.862	Destabilizing	0.055	N	0.596	neutral	N	0.506056357	None	None	I
P/S	0.2742	likely_benign	0.2371	benign	-1.667	Destabilizing	0.012	N	0.396	neutral	N	0.475924234	None	None	I
P/T	0.2916	likely_benign	0.255	benign	-1.522	Destabilizing	0.024	N	0.389	neutral	N	0.476684702	None	None	I
P/V	0.3107	likely_benign	0.2771	benign	-1.052	Destabilizing	None	N	0.377	neutral	None	None	None	None	I
P/W	0.8758	likely_pathogenic	0.8653	pathogenic	-1.511	Destabilizing	0.864	D	0.579	neutral	None	None	None	None	I
P/Y	0.7291	likely_pathogenic	0.7114	pathogenic	-1.208	Destabilizing	0.038	N	0.594	neutral	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.