TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24754	74485;74486;74487	chr2:178571872;178571871;178571870	chr2:179436599;179436598;179436597
N2AB	23113	69562;69563;69564	chr2:178571872;178571871;178571870	chr2:179436599;179436598;179436597
N2A	22186	66781;66782;66783	chr2:178571872;178571871;178571870	chr2:179436599;179436598;179436597
N2B	15689	47290;47291;47292	chr2:178571872;178571871;178571870	chr2:179436599;179436598;179436597
Novex-1	15814	47665;47666;47667	chr2:178571872;178571871;178571870	chr2:179436599;179436598;179436597
Novex-2	15881	47866;47867;47868	chr2:178571872;178571871;178571870	chr2:179436599;179436598;179436597
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Ig-133
• Domain position: 39
• Structural Position: 55
• Q(SASA): 0.4005
• 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
V/A	rs12616029	-0.829	0.012	N	0.227	0.1	None	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
V/A	rs12616029	-0.829	0.012	N	0.227	0.1	None	gnomAD-4.0.0	9.55107E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.71567E-05	0	0
V/I	None	None	None	N	0.175	0.074	0.202949470691	gnomAD-4.0.0	1.5919E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85954E-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	0.1011	likely_benign	0.1001	benign	-0.695	Destabilizing	0.012	N	0.227	neutral	N	0.454595974	None	None	N
V/C	0.4229	ambiguous	0.4157	ambiguous	-0.376	Destabilizing	0.864	D	0.337	neutral	None	None	None	None	N
V/D	0.1641	likely_benign	0.1615	benign	-0.818	Destabilizing	0.038	N	0.424	neutral	None	None	None	None	N
V/E	0.1453	likely_benign	0.1408	benign	-0.938	Destabilizing	0.055	N	0.429	neutral	N	0.433988628	None	None	N
V/F	0.1153	likely_benign	0.114	benign	-0.96	Destabilizing	0.12	N	0.362	neutral	None	None	None	None	N
V/G	0.1306	likely_benign	0.1272	benign	-0.848	Destabilizing	0.055	N	0.409	neutral	N	0.480494496	None	None	N
V/H	0.2534	likely_benign	0.2498	benign	-0.53	Destabilizing	0.001	N	0.372	neutral	None	None	None	None	N
V/I	0.0633	likely_benign	0.0625	benign	-0.434	Destabilizing	None	N	0.175	neutral	N	0.471432295	None	None	N
V/K	0.1756	likely_benign	0.1681	benign	-0.637	Destabilizing	0.072	N	0.432	neutral	None	None	None	None	N
V/L	0.0916	likely_benign	0.0895	benign	-0.434	Destabilizing	None	N	0.146	neutral	N	0.467122554	None	None	N
V/M	0.0795	likely_benign	0.0767	benign	-0.247	Destabilizing	0.214	N	0.294	neutral	None	None	None	None	N
V/N	0.1071	likely_benign	0.1076	benign	-0.237	Destabilizing	0.001	N	0.305	neutral	None	None	None	None	N
V/P	0.7838	likely_pathogenic	0.7983	pathogenic	-0.487	Destabilizing	0.356	N	0.425	neutral	None	None	None	None	N
V/Q	0.1401	likely_benign	0.1363	benign	-0.537	Destabilizing	0.356	N	0.418	neutral	None	None	None	None	N
V/R	0.1723	likely_benign	0.1681	benign	-0.04	Destabilizing	0.214	N	0.443	neutral	None	None	None	None	N
V/S	0.1026	likely_benign	0.1015	benign	-0.516	Destabilizing	0.038	N	0.345	neutral	None	None	None	None	N
V/T	0.0962	likely_benign	0.0944	benign	-0.548	Destabilizing	None	N	0.143	neutral	None	None	None	None	N
V/W	0.5854	likely_pathogenic	0.571	pathogenic	-1.069	Destabilizing	0.864	D	0.426	neutral	None	None	None	None	N
V/Y	0.2638	likely_benign	0.2601	benign	-0.778	Destabilizing	0.214	N	0.359	neutral	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.