TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28533	85822;85823;85824	chr2:178560535;178560534;178560533	chr2:179425262;179425261;179425260
N2AB	26892	80899;80900;80901	chr2:178560535;178560534;178560533	chr2:179425262;179425261;179425260
N2A	25965	78118;78119;78120	chr2:178560535;178560534;178560533	chr2:179425262;179425261;179425260
N2B	19468	58627;58628;58629	chr2:178560535;178560534;178560533	chr2:179425262;179425261;179425260
Novex-1	19593	59002;59003;59004	chr2:178560535;178560534;178560533	chr2:179425262;179425261;179425260
Novex-2	19660	59203;59204;59205	chr2:178560535;178560534;178560533	chr2:179425262;179425261;179425260
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-95
• Domain position: 84
• Structural Position: 117
• Q(SASA): 0.6002
• 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/I	None	None	0.826	N	0.443	0.159	0.408307896497	gnomAD-4.0.0	1.59252E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85953E-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	0.0898	likely_benign	0.0892	benign	-0.859	Destabilizing	0.826	D	0.471	neutral	N	0.470415496	None	None	N
V/C	0.5382	ambiguous	0.5697	pathogenic	-0.888	Destabilizing	0.999	D	0.577	neutral	None	None	None	None	N
V/D	0.2154	likely_benign	0.2063	benign	-0.121	Destabilizing	0.015	N	0.463	neutral	N	0.468122646	None	None	N
V/E	0.1711	likely_benign	0.1678	benign	-0.192	Destabilizing	0.884	D	0.57	neutral	None	None	None	None	N
V/F	0.1365	likely_benign	0.1262	benign	-0.82	Destabilizing	0.996	D	0.602	neutral	N	0.465160132	None	None	N
V/G	0.1637	likely_benign	0.1594	benign	-1.059	Destabilizing	0.959	D	0.591	neutral	N	0.475061633	None	None	N
V/H	0.3639	ambiguous	0.3703	ambiguous	-0.454	Destabilizing	0.999	D	0.649	neutral	None	None	None	None	N
V/I	0.0717	likely_benign	0.0736	benign	-0.461	Destabilizing	0.826	D	0.443	neutral	N	0.434052051	None	None	N
V/K	0.1672	likely_benign	0.1644	benign	-0.547	Destabilizing	0.939	D	0.641	neutral	None	None	None	None	N
V/L	0.1463	likely_benign	0.1527	benign	-0.461	Destabilizing	0.826	D	0.455	neutral	N	0.478880264	None	None	N
V/M	0.1123	likely_benign	0.1159	benign	-0.501	Destabilizing	0.997	D	0.604	neutral	None	None	None	None	N
V/N	0.1946	likely_benign	0.1905	benign	-0.337	Destabilizing	0.939	D	0.639	neutral	None	None	None	None	N
V/P	0.2184	likely_benign	0.251	benign	-0.557	Destabilizing	0.997	D	0.646	neutral	None	None	None	None	N
V/Q	0.1963	likely_benign	0.1951	benign	-0.552	Destabilizing	0.991	D	0.661	neutral	None	None	None	None	N
V/R	0.1431	likely_benign	0.1395	benign	-0.044	Destabilizing	0.991	D	0.662	neutral	None	None	None	None	N
V/S	0.133	likely_benign	0.1336	benign	-0.871	Destabilizing	0.884	D	0.58	neutral	None	None	None	None	N
V/T	0.106	likely_benign	0.1081	benign	-0.827	Destabilizing	0.17	N	0.226	neutral	None	None	None	None	N
V/W	0.6241	likely_pathogenic	0.6213	pathogenic	-0.849	Destabilizing	0.999	D	0.693	prob.neutral	None	None	None	None	N
V/Y	0.3634	ambiguous	0.3695	ambiguous	-0.564	Destabilizing	0.997	D	0.591	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.