TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29380	88363;88364;88365	chr2:178557016;178557015;178557014	chr2:179421743;179421742;179421741
N2AB	27739	83440;83441;83442	chr2:178557016;178557015;178557014	chr2:179421743;179421742;179421741
N2A	26812	80659;80660;80661	chr2:178557016;178557015;178557014	chr2:179421743;179421742;179421741
N2B	20315	61168;61169;61170	chr2:178557016;178557015;178557014	chr2:179421743;179421742;179421741
Novex-1	20440	61543;61544;61545	chr2:178557016;178557015;178557014	chr2:179421743;179421742;179421741
Novex-2	20507	61744;61745;61746	chr2:178557016;178557015;178557014	chr2:179421743;179421742;179421741
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Fn3-102
• Domain position: 46
• Structural Position: 63
• Q(SASA): 0.438
• 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/D	rs1701762557	None	0.999	N	0.657	0.377	0.368369118721	gnomAD-4.0.0	1.27307E-05	None	None	None	None	N	None	0	0	None	0	2.22321E-04	None	0	0	0	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	0.4439	ambiguous	0.3208	benign	-0.703	Destabilizing	0.767	D	0.395	neutral	N	0.496148991	None	None	N
G/C	0.6055	likely_pathogenic	0.4617	ambiguous	-0.851	Destabilizing	1.0	D	0.791	deleterious	D	0.533878439	None	None	N
G/D	0.7461	likely_pathogenic	0.6282	pathogenic	-1.243	Destabilizing	0.999	D	0.657	neutral	N	0.476905874	None	None	N
G/E	0.7447	likely_pathogenic	0.6162	pathogenic	-1.374	Destabilizing	0.999	D	0.696	prob.neutral	None	None	None	None	N
G/F	0.9447	likely_pathogenic	0.8909	pathogenic	-1.24	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
G/H	0.8484	likely_pathogenic	0.7409	pathogenic	-1.177	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
G/I	0.8509	likely_pathogenic	0.7314	pathogenic	-0.607	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
G/K	0.8114	likely_pathogenic	0.7033	pathogenic	-1.358	Destabilizing	0.999	D	0.697	prob.neutral	None	None	None	None	N
G/L	0.8928	likely_pathogenic	0.7984	pathogenic	-0.607	Destabilizing	0.999	D	0.744	deleterious	None	None	None	None	N
G/M	0.8919	likely_pathogenic	0.8029	pathogenic	-0.452	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
G/N	0.7106	likely_pathogenic	0.5938	pathogenic	-0.866	Destabilizing	0.999	D	0.648	neutral	None	None	None	None	N
G/P	0.9803	likely_pathogenic	0.9642	pathogenic	-0.602	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
G/Q	0.7609	likely_pathogenic	0.6383	pathogenic	-1.163	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
G/R	0.7279	likely_pathogenic	0.5791	pathogenic	-0.86	Destabilizing	0.999	D	0.737	prob.delet.	N	0.49690946	None	None	N
G/S	0.2577	likely_benign	0.1846	benign	-0.993	Destabilizing	0.905	D	0.375	neutral	N	0.499954543	None	None	N
G/T	0.5819	likely_pathogenic	0.4419	ambiguous	-1.067	Destabilizing	0.998	D	0.628	neutral	None	None	None	None	N
G/V	0.7615	likely_pathogenic	0.6097	pathogenic	-0.602	Destabilizing	0.999	D	0.745	deleterious	N	0.495326071	None	None	N
G/W	0.9016	likely_pathogenic	0.8095	pathogenic	-1.465	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
G/Y	0.8847	likely_pathogenic	0.7993	pathogenic	-1.137	Destabilizing	1.0	D	0.802	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.