TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24298	73117;73118;73119	chr2:178573240;178573239;178573238	chr2:179437967;179437966;179437965
N2AB	22657	68194;68195;68196	chr2:178573240;178573239;178573238	chr2:179437967;179437966;179437965
N2A	21730	65413;65414;65415	chr2:178573240;178573239;178573238	chr2:179437967;179437966;179437965
N2B	15233	45922;45923;45924	chr2:178573240;178573239;178573238	chr2:179437967;179437966;179437965
Novex-1	15358	46297;46298;46299	chr2:178573240;178573239;178573238	chr2:179437967;179437966;179437965
Novex-2	15425	46498;46499;46500	chr2:178573240;178573239;178573238	chr2:179437967;179437966;179437965
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: M
• RefSeq wild type transcript codon: ATG
• RefSeq wild type template codon: TAC
• Domain: Fn3-64
• Domain position: 77
• Structural Position: 109
• Q(SASA): 0.1409
• 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
M/I	None	None	0.003	N	0.294	0.119	0.358948522604	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	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
M/A	0.2918	likely_benign	0.2265	benign	-2.395	Highly Destabilizing	0.063	N	0.527	neutral	None	None	None	None	N
M/C	0.5463	ambiguous	0.5262	ambiguous	-2.374	Highly Destabilizing	0.942	D	0.653	neutral	None	None	None	None	N
M/D	0.919	likely_pathogenic	0.8707	pathogenic	-2.396	Highly Destabilizing	0.428	N	0.689	prob.neutral	None	None	None	None	N
M/E	0.6208	likely_pathogenic	0.5459	ambiguous	-2.227	Highly Destabilizing	0.134	N	0.639	neutral	None	None	None	None	N
M/F	0.2784	likely_benign	0.2443	benign	-0.925	Destabilizing	0.001	N	0.218	neutral	None	None	None	None	N
M/G	0.6351	likely_pathogenic	0.5351	ambiguous	-2.791	Highly Destabilizing	0.134	N	0.643	neutral	None	None	None	None	N
M/H	0.4468	ambiguous	0.4013	ambiguous	-2.297	Highly Destabilizing	0.942	D	0.644	neutral	None	None	None	None	N
M/I	0.3911	ambiguous	0.3053	benign	-1.272	Destabilizing	0.003	N	0.294	neutral	N	0.433457405	None	None	N
M/K	0.1713	likely_benign	0.1586	benign	-1.698	Destabilizing	0.001	N	0.418	neutral	N	0.406924165	None	None	N
M/L	0.1428	likely_benign	0.1257	benign	-1.272	Destabilizing	None	N	0.223	neutral	N	0.424395205	None	None	N
M/N	0.5652	likely_pathogenic	0.463	ambiguous	-1.896	Destabilizing	0.428	N	0.681	prob.neutral	None	None	None	None	N
M/P	0.992	likely_pathogenic	0.9836	pathogenic	-1.629	Destabilizing	0.603	D	0.663	neutral	None	None	None	None	N
M/Q	0.235	likely_benign	0.2181	benign	-1.725	Destabilizing	0.428	N	0.625	neutral	None	None	None	None	N
M/R	0.2005	likely_benign	0.1759	benign	-1.564	Destabilizing	0.22	N	0.683	prob.neutral	N	0.406750807	None	None	N
M/S	0.2601	likely_benign	0.2114	benign	-2.425	Highly Destabilizing	0.004	N	0.382	neutral	None	None	None	None	N
M/T	0.134	likely_benign	0.1096	benign	-2.156	Highly Destabilizing	0.001	N	0.373	neutral	N	0.386434249	None	None	N
M/V	0.1191	likely_benign	0.103	benign	-1.629	Destabilizing	0.022	N	0.513	neutral	N	0.443442325	None	None	N
M/W	0.6285	likely_pathogenic	0.5741	pathogenic	-1.215	Destabilizing	0.942	D	0.652	neutral	None	None	None	None	N
M/Y	0.5022	ambiguous	0.4552	ambiguous	-1.23	Destabilizing	0.273	N	0.689	prob.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.