TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5999	18220;18221;18222	chr2:178730538;178730537;178730536	chr2:179595265;179595264;179595263
N2AB	5682	17269;17270;17271	chr2:178730538;178730537;178730536	chr2:179595265;179595264;179595263
N2A	4755	14488;14489;14490	chr2:178730538;178730537;178730536	chr2:179595265;179595264;179595263
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: H
• RefSeq wild type transcript codon: CAC
• RefSeq wild type template codon: GTG
• Domain: Ig-43
• Domain position: 81
• Structural Position: 165
• Q(SASA): 0.7424
• 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
H/N	None	None	0.159	N	0.217	0.113	0.183819452728	gnomAD-4.0.0	1.59278E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86203E-06	0	0
H/Y	rs1443927165	0.952	0.866	N	0.43	0.138	0.330069100803	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
H/Y	rs1443927165	0.952	0.866	N	0.43	0.138	0.330069100803	gnomAD-4.0.0	1.59278E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43365E-05	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
H/A	0.1565	likely_benign	0.1786	benign	-0.059	Destabilizing	0.003	N	0.22	neutral	None	None	None	None	N
H/C	0.1461	likely_benign	0.1541	benign	0.515	Stabilizing	0.968	D	0.477	neutral	None	None	None	None	N
H/D	0.1269	likely_benign	0.1523	benign	0.011	Stabilizing	0.302	N	0.372	neutral	N	0.437434365	None	None	N
H/E	0.1594	likely_benign	0.1813	benign	0.028	Stabilizing	0.111	N	0.168	neutral	None	None	None	None	N
H/F	0.2255	likely_benign	0.2341	benign	0.438	Stabilizing	0.896	D	0.491	neutral	None	None	None	None	N
H/G	0.1983	likely_benign	0.226	benign	-0.334	Destabilizing	0.111	N	0.351	neutral	None	None	None	None	N
H/I	0.1969	likely_benign	0.2109	benign	0.639	Stabilizing	0.582	D	0.533	neutral	None	None	None	None	N
H/K	0.1184	likely_benign	0.1328	benign	-0.066	Destabilizing	0.001	N	0.168	neutral	None	None	None	None	N
H/L	0.1032	likely_benign	0.1079	benign	0.639	Stabilizing	0.159	N	0.431	neutral	N	0.486343033	None	None	N
H/M	0.3111	likely_benign	0.319	benign	0.559	Stabilizing	0.968	D	0.469	neutral	None	None	None	None	N
H/N	0.0668	likely_benign	0.0764	benign	0.083	Stabilizing	0.159	N	0.217	neutral	N	0.4384158	None	None	N
H/P	0.382	ambiguous	0.4663	ambiguous	0.431	Stabilizing	0.468	N	0.488	neutral	N	0.486516391	None	None	N
H/Q	0.0874	likely_benign	0.0948	benign	0.146	Stabilizing	0.302	N	0.335	neutral	N	0.430121604	None	None	N
H/R	0.0639	likely_benign	0.0693	benign	-0.473	Destabilizing	None	N	0.143	neutral	N	0.431335112	None	None	N
H/S	0.1042	likely_benign	0.1203	benign	0.078	Stabilizing	0.003	N	0.165	neutral	None	None	None	None	N
H/T	0.1189	likely_benign	0.1368	benign	0.187	Stabilizing	0.003	N	0.219	neutral	None	None	None	None	N
H/V	0.1621	likely_benign	0.17	benign	0.431	Stabilizing	0.365	N	0.461	neutral	None	None	None	None	N
H/W	0.3362	likely_benign	0.3466	ambiguous	0.469	Stabilizing	0.991	D	0.461	neutral	None	None	None	None	N
H/Y	0.0864	likely_benign	0.0932	benign	0.793	Stabilizing	0.866	D	0.43	neutral	N	0.46783463	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.