TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6935	21028;21029;21030	chr2:178725401;178725400;178725399	chr2:179590128;179590127;179590126
N2AB	6618	20077;20078;20079	chr2:178725401;178725400;178725399	chr2:179590128;179590127;179590126
N2A	5691	17296;17297;17298	chr2:178725401;178725400;178725399	chr2:179590128;179590127;179590126
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-53
• Domain position: 82
• Structural Position: 165
• Q(SASA): 0.5412
• Predicted PPI site: I

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	rs770899268	-0.145	0.001	N	0.191	0.132	0.241664281697	gnomAD-2.1.1	1.14E-05	None	None	None	None	I	None	1.26914E-04	0	None	0	0	None	0	None	0	0	0
M/I	rs770899268	-0.145	0.001	N	0.191	0.132	0.241664281697	gnomAD-3.1.2	2.63E-05	None	None	None	None	I	None	9.65E-05	0	0	0	0	None	0	0	0	0	0
M/I	rs770899268	-0.145	0.001	N	0.191	0.132	0.241664281697	gnomAD-4.0.0	6.54127E-06	None	None	None	None	I	None	8.48119E-05	0	None	0	0	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
M/A	0.273	likely_benign	0.2165	benign	-1.22	Destabilizing	None	N	0.164	neutral	None	None	None	None	I
M/C	0.7105	likely_pathogenic	0.6316	pathogenic	-1.051	Destabilizing	0.245	N	0.439	neutral	None	None	None	None	I
M/D	0.7059	likely_pathogenic	0.627	pathogenic	-0.33	Destabilizing	0.018	N	0.499	neutral	None	None	None	None	I
M/E	0.3441	ambiguous	0.2938	benign	-0.342	Destabilizing	0.004	N	0.385	neutral	None	None	None	None	I
M/F	0.2495	likely_benign	0.2042	benign	-0.431	Destabilizing	0.018	N	0.387	neutral	None	None	None	None	I
M/G	0.4592	ambiguous	0.3862	ambiguous	-1.474	Destabilizing	0.004	N	0.403	neutral	None	None	None	None	I
M/H	0.4295	ambiguous	0.3519	ambiguous	-0.5	Destabilizing	0.245	N	0.496	neutral	None	None	None	None	I
M/I	0.1989	likely_benign	0.1649	benign	-0.603	Destabilizing	0.001	N	0.191	neutral	N	0.494962516	None	None	I
M/K	0.1689	likely_benign	0.1398	benign	-0.25	Destabilizing	0.003	N	0.321	neutral	N	0.45022473	None	None	I
M/L	0.1248	likely_benign	0.1097	benign	-0.603	Destabilizing	0.001	N	0.155	neutral	D	0.531787321	None	None	I
M/N	0.3413	ambiguous	0.2625	benign	-0.112	Destabilizing	0.018	N	0.479	neutral	None	None	None	None	I
M/P	0.7867	likely_pathogenic	0.7279	pathogenic	-0.78	Destabilizing	0.037	N	0.519	neutral	None	None	None	None	I
M/Q	0.1897	likely_benign	0.1607	benign	-0.266	Destabilizing	0.001	N	0.137	neutral	None	None	None	None	I
M/R	0.1807	likely_benign	0.1505	benign	0.321	Stabilizing	0.014	N	0.479	neutral	N	0.501733773	None	None	I
M/S	0.2187	likely_benign	0.1695	benign	-0.643	Destabilizing	None	N	0.159	neutral	None	None	None	None	I
M/T	0.1327	likely_benign	0.0962	benign	-0.553	Destabilizing	None	N	0.169	neutral	N	0.436740932	None	None	I
M/V	0.0788	likely_benign	0.0727	benign	-0.78	Destabilizing	None	N	0.119	neutral	N	0.442090823	None	None	I
M/W	0.5094	ambiguous	0.463	ambiguous	-0.348	Destabilizing	None	N	0.186	neutral	None	None	None	None	I
M/Y	0.474	ambiguous	0.4073	ambiguous	-0.328	Destabilizing	0.044	N	0.487	neutral	None	None	None	None	I

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.