TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20860	62803;62804;62805	chr2:178589147;178589146;178589145	chr2:179453874;179453873;179453872
N2AB	19219	57880;57881;57882	chr2:178589147;178589146;178589145	chr2:179453874;179453873;179453872
N2A	18292	55099;55100;55101	chr2:178589147;178589146;178589145	chr2:179453874;179453873;179453872
N2B	11795	35608;35609;35610	chr2:178589147;178589146;178589145	chr2:179453874;179453873;179453872
Novex-1	11920	35983;35984;35985	chr2:178589147;178589146;178589145	chr2:179453874;179453873;179453872
Novex-2	11987	36184;36185;36186	chr2:178589147;178589146;178589145	chr2:179453874;179453873;179453872
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-122
• Domain position: 92
• Structural Position: 175
• Q(SASA): 0.4206
• 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
N/S	rs1405326036	None	0.008	N	0.085	0.122	0.229264304666	gnomAD-4.0.0	3.42224E-06	None	None	None	None	N	None	0	0	None	0	2.52653E-05	None	0	0	1.79913E-06	0	3.314E-05

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
N/A	0.2706	likely_benign	0.2055	benign	-0.903	Destabilizing	0.055	N	0.421	neutral	None	None	None	None	N
N/C	0.2995	likely_benign	0.2679	benign	-0.087	Destabilizing	0.958	D	0.466	neutral	None	None	None	None	N
N/D	0.3134	likely_benign	0.3052	benign	-0.419	Destabilizing	0.042	N	0.283	neutral	D	0.52413063	None	None	N
N/E	0.5063	ambiguous	0.4732	ambiguous	-0.355	Destabilizing	0.004	N	0.131	neutral	None	None	None	None	N
N/F	0.567	likely_pathogenic	0.4916	ambiguous	-0.738	Destabilizing	0.497	N	0.52	neutral	None	None	None	None	N
N/G	0.4694	ambiguous	0.4107	ambiguous	-1.206	Destabilizing	0.104	N	0.257	neutral	None	None	None	None	N
N/H	0.1102	likely_benign	0.1008	benign	-0.919	Destabilizing	0.822	D	0.425	neutral	N	0.517204657	None	None	N
N/I	0.1768	likely_benign	0.1215	benign	-0.148	Destabilizing	None	N	0.291	neutral	N	0.511470764	None	None	N
N/K	0.3789	ambiguous	0.3419	ambiguous	-0.202	Destabilizing	0.175	N	0.249	neutral	N	0.507600952	None	None	N
N/L	0.2083	likely_benign	0.1598	benign	-0.148	Destabilizing	0.02	N	0.444	neutral	None	None	None	None	N
N/M	0.2628	likely_benign	0.2043	benign	0.309	Stabilizing	0.497	N	0.461	neutral	None	None	None	None	N
N/P	0.9702	likely_pathogenic	0.9627	pathogenic	-0.371	Destabilizing	0.667	D	0.504	neutral	None	None	None	None	N
N/Q	0.35	ambiguous	0.306	benign	-0.852	Destabilizing	0.22	N	0.385	neutral	None	None	None	None	N
N/R	0.3823	ambiguous	0.3542	ambiguous	-0.132	Destabilizing	0.22	N	0.359	neutral	None	None	None	None	N
N/S	0.0968	likely_benign	0.0846	benign	-0.801	Destabilizing	0.008	N	0.085	neutral	N	0.508987819	None	None	N
N/T	0.1056	likely_benign	0.0862	benign	-0.554	Destabilizing	0.001	N	0.087	neutral	N	0.445379058	None	None	N
N/V	0.1839	likely_benign	0.1336	benign	-0.371	Destabilizing	0.02	N	0.444	neutral	None	None	None	None	N
N/W	0.8133	likely_pathogenic	0.7745	pathogenic	-0.452	Destabilizing	0.958	D	0.526	neutral	None	None	None	None	N
N/Y	0.2178	likely_benign	0.1984	benign	-0.269	Destabilizing	0.602	D	0.485	neutral	N	0.493049844	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.