TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29231	87916;87917;87918	chr2:178557663;178557662;178557661	chr2:179422390;179422389;179422388
N2AB	27590	82993;82994;82995	chr2:178557663;178557662;178557661	chr2:179422390;179422389;179422388
N2A	26663	80212;80213;80214	chr2:178557663;178557662;178557661	chr2:179422390;179422389;179422388
N2B	20166	60721;60722;60723	chr2:178557663;178557662;178557661	chr2:179422390;179422389;179422388
Novex-1	20291	61096;61097;61098	chr2:178557663;178557662;178557661	chr2:179422390;179422389;179422388
Novex-2	20358	61297;61298;61299	chr2:178557663;178557662;178557661	chr2:179422390;179422389;179422388
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Fn3-100
• Domain position: 95
• Structural Position: 130
• Q(SASA): 0.3816
• 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
V/L	None	None	0.429	N	0.567	0.1	0.49741755877	gnomAD-4.0.0	3.18283E-06	None	None	None	None	I	None	0	0	None	0	0	None	1.88232E-05	0	2.85801E-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
V/A	0.4059	ambiguous	0.3738	ambiguous	-2.194	Highly Destabilizing	0.914	D	0.597	neutral	N	0.366154978	None	None	I
V/C	0.8772	likely_pathogenic	0.8724	pathogenic	-2.219	Highly Destabilizing	0.999	D	0.748	deleterious	None	None	None	None	I
V/D	0.9896	likely_pathogenic	0.9867	pathogenic	-2.996	Highly Destabilizing	0.996	D	0.833	deleterious	N	0.491866123	None	None	I
V/E	0.9751	likely_pathogenic	0.9683	pathogenic	-2.824	Highly Destabilizing	0.997	D	0.824	deleterious	None	None	None	None	I
V/F	0.7553	likely_pathogenic	0.7564	pathogenic	-1.317	Destabilizing	0.974	D	0.71	prob.delet.	N	0.469959525	None	None	I
V/G	0.7593	likely_pathogenic	0.7404	pathogenic	-2.661	Highly Destabilizing	0.987	D	0.789	deleterious	N	0.468228459	None	None	I
V/H	0.9911	likely_pathogenic	0.9895	pathogenic	-2.182	Highly Destabilizing	0.999	D	0.849	deleterious	None	None	None	None	I
V/I	0.1016	likely_benign	0.1135	benign	-0.904	Destabilizing	0.032	N	0.28	neutral	N	0.456006191	None	None	I
V/K	0.979	likely_pathogenic	0.9732	pathogenic	-1.804	Destabilizing	0.99	D	0.821	deleterious	None	None	None	None	I
V/L	0.4396	ambiguous	0.4672	ambiguous	-0.904	Destabilizing	0.429	N	0.567	neutral	N	0.501143835	None	None	I
V/M	0.4606	ambiguous	0.4401	ambiguous	-1.252	Destabilizing	0.98	D	0.717	prob.delet.	None	None	None	None	I
V/N	0.94	likely_pathogenic	0.9265	pathogenic	-2.106	Highly Destabilizing	0.997	D	0.863	deleterious	None	None	None	None	I
V/P	0.8201	likely_pathogenic	0.8601	pathogenic	-1.308	Destabilizing	0.997	D	0.861	deleterious	None	None	None	None	I
V/Q	0.9667	likely_pathogenic	0.9571	pathogenic	-2.055	Highly Destabilizing	0.997	D	0.872	deleterious	None	None	None	None	I
V/R	0.9594	likely_pathogenic	0.9511	pathogenic	-1.519	Destabilizing	0.997	D	0.855	deleterious	None	None	None	None	I
V/S	0.7953	likely_pathogenic	0.7412	pathogenic	-2.691	Highly Destabilizing	0.99	D	0.811	deleterious	None	None	None	None	I
V/T	0.687	likely_pathogenic	0.6206	pathogenic	-2.388	Highly Destabilizing	0.933	D	0.717	prob.delet.	None	None	None	None	I
V/W	0.9949	likely_pathogenic	0.9944	pathogenic	-1.705	Destabilizing	0.999	D	0.827	deleterious	None	None	None	None	I
V/Y	0.9788	likely_pathogenic	0.9778	pathogenic	-1.405	Destabilizing	0.99	D	0.741	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.