TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8213	24862;24863;24864	chr2:178718469;178718468;178718467	chr2:179583196;179583195;179583194
N2AB	7896	23911;23912;23913	chr2:178718469;178718468;178718467	chr2:179583196;179583195;179583194
N2A	6969	21130;21131;21132	chr2:178718469;178718468;178718467	chr2:179583196;179583195;179583194
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: Q
• RefSeq wild type transcript codon: CAA
• RefSeq wild type template codon: GTT
• Domain: Ig-67
• Domain position: 43
• Structural Position: 70
• Q(SASA): 0.7729
• 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
Q/H	rs397517510	-0.161	0.002	N	0.171	0.078	0.128392430309	gnomAD-2.1.1	3.57E-05	None	None	None	None	I	None	0	2.83E-05	None	0	0	None	0	None	0	7.05E-05	0
Q/H	rs397517510	-0.161	0.002	N	0.171	0.078	0.128392430309	gnomAD-3.1.2	8.55E-05	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.91165E-04	0	0
Q/H	rs397517510	-0.161	0.002	N	0.171	0.078	0.128392430309	gnomAD-4.0.0	1.05974E-04	None	None	None	None	I	None	0	1.66756E-05	None	0	0	None	0	0	1.30537E-04	0	2.56205E-04
Q/K	None	None	0.183	D	0.199	0.265	0.212008924253	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.625E-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
Q/A	0.1526	likely_benign	0.1582	benign	-0.209	Destabilizing	0.001	N	0.118	neutral	None	None	None	None	I
Q/C	0.6513	likely_pathogenic	0.6369	pathogenic	0.252	Stabilizing	0.94	D	0.256	neutral	None	None	None	None	I
Q/D	0.2814	likely_benign	0.2971	benign	0.114	Stabilizing	0.228	N	0.138	neutral	None	None	None	None	I
Q/E	0.0772	likely_benign	0.0785	benign	0.065	Stabilizing	0.101	N	0.17	neutral	N	0.471930941	None	None	I
Q/F	0.6018	likely_pathogenic	0.6185	pathogenic	-0.609	Destabilizing	0.716	D	0.336	neutral	None	None	None	None	I
Q/G	0.207	likely_benign	0.2046	benign	-0.337	Destabilizing	0.001	N	0.121	neutral	None	None	None	None	I
Q/H	0.1952	likely_benign	0.198	benign	-0.441	Destabilizing	0.002	N	0.171	neutral	N	0.499755047	None	None	I
Q/I	0.3649	ambiguous	0.3696	ambiguous	0.032	Stabilizing	0.264	N	0.365	neutral	None	None	None	None	I
Q/K	0.0968	likely_benign	0.0884	benign	0.238	Stabilizing	0.183	N	0.199	neutral	D	0.527997654	None	None	I
Q/L	0.1467	likely_benign	0.1517	benign	0.032	Stabilizing	0.101	N	0.219	neutral	N	0.508643889	None	None	I
Q/M	0.3617	ambiguous	0.3777	ambiguous	0.396	Stabilizing	0.836	D	0.161	neutral	None	None	None	None	I
Q/N	0.2259	likely_benign	0.2409	benign	-0.058	Destabilizing	0.264	N	0.135	neutral	None	None	None	None	I
Q/P	0.0638	likely_benign	0.0659	benign	-0.024	Destabilizing	0.001	N	0.165	neutral	N	0.429046955	None	None	I
Q/R	0.1012	likely_benign	0.0983	benign	0.278	Stabilizing	0.351	N	0.173	neutral	N	0.514953786	None	None	I
Q/S	0.156	likely_benign	0.1697	benign	-0.043	Destabilizing	0.012	N	0.153	neutral	None	None	None	None	I
Q/T	0.1551	likely_benign	0.1676	benign	0.051	Stabilizing	0.129	N	0.257	neutral	None	None	None	None	I
Q/V	0.2412	likely_benign	0.2472	benign	-0.024	Destabilizing	0.004	N	0.161	neutral	None	None	None	None	I
Q/W	0.5154	ambiguous	0.491	ambiguous	-0.626	Destabilizing	0.983	D	0.257	neutral	None	None	None	None	I
Q/Y	0.41	ambiguous	0.4106	ambiguous	-0.337	Destabilizing	0.264	N	0.337	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.