TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27218	81877;81878;81879	chr2:178564480;178564479;178564478	chr2:179429207;179429206;179429205
N2AB	25577	76954;76955;76956	chr2:178564480;178564479;178564478	chr2:179429207;179429206;179429205
N2A	24650	74173;74174;74175	chr2:178564480;178564479;178564478	chr2:179429207;179429206;179429205
N2B	18153	54682;54683;54684	chr2:178564480;178564479;178564478	chr2:179429207;179429206;179429205
Novex-1	18278	55057;55058;55059	chr2:178564480;178564479;178564478	chr2:179429207;179429206;179429205
Novex-2	18345	55258;55259;55260	chr2:178564480;178564479;178564478	chr2:179429207;179429206;179429205
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: Fn3-86
• Domain position: 49
• Structural Position: 66
• Q(SASA): 0.503
• 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/T	rs1332904652	None	0.007	N	0.22	0.295	0.57631073843	gnomAD-4.0.0	2.40065E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.62501E-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	0.814	likely_pathogenic	0.7931	pathogenic	-1.786	Destabilizing	0.373	N	0.423	neutral	None	None	None	None	N
M/C	0.8683	likely_pathogenic	0.8661	pathogenic	-1.211	Destabilizing	0.996	D	0.411	neutral	None	None	None	None	N
M/D	0.9783	likely_pathogenic	0.977	pathogenic	-0.588	Destabilizing	0.91	D	0.407	neutral	None	None	None	None	N
M/E	0.8361	likely_pathogenic	0.8189	pathogenic	-0.555	Destabilizing	0.742	D	0.397	neutral	None	None	None	None	N
M/F	0.62	likely_pathogenic	0.5759	pathogenic	-0.715	Destabilizing	0.953	D	0.42	neutral	None	None	None	None	N
M/G	0.9018	likely_pathogenic	0.8934	pathogenic	-2.101	Highly Destabilizing	0.742	D	0.403	neutral	None	None	None	None	N
M/H	0.8332	likely_pathogenic	0.8157	pathogenic	-1.11	Destabilizing	0.996	D	0.411	neutral	None	None	None	None	N
M/I	0.6024	likely_pathogenic	0.564	ambiguous	-0.97	Destabilizing	0.684	D	0.488	neutral	N	0.482731432	None	None	N
M/K	0.5543	ambiguous	0.5012	ambiguous	-0.673	Destabilizing	0.684	D	0.426	neutral	N	0.480248488	None	None	N
M/L	0.1897	likely_benign	0.1686	benign	-0.97	Destabilizing	0.164	N	0.211	neutral	N	0.435054916	None	None	N
M/N	0.7918	likely_pathogenic	0.7924	pathogenic	-0.514	Destabilizing	0.91	D	0.402	neutral	None	None	None	None	N
M/P	0.9927	likely_pathogenic	0.9913	pathogenic	-1.216	Destabilizing	0.953	D	0.415	neutral	None	None	None	None	N
M/Q	0.4288	ambiguous	0.4418	ambiguous	-0.595	Destabilizing	0.953	D	0.42	neutral	None	None	None	None	N
M/R	0.5776	likely_pathogenic	0.5124	ambiguous	-0.152	Destabilizing	0.884	D	0.409	neutral	N	0.482384716	None	None	N
M/S	0.77	likely_pathogenic	0.7747	pathogenic	-1.128	Destabilizing	0.59	D	0.451	neutral	None	None	None	None	N
M/T	0.5873	likely_pathogenic	0.592	pathogenic	-0.988	Destabilizing	0.007	N	0.22	neutral	N	0.470879643	None	None	N
M/V	0.1905	likely_benign	0.1789	benign	-1.216	Destabilizing	0.309	N	0.452	neutral	N	0.448752145	None	None	N
M/W	0.9012	likely_pathogenic	0.872	pathogenic	-0.641	Destabilizing	0.996	D	0.435	neutral	None	None	None	None	N
M/Y	0.8347	likely_pathogenic	0.8097	pathogenic	-0.697	Destabilizing	0.984	D	0.423	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.