TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6077	18454;18455;18456	chr2:178730171;178730170;178730169	chr2:179594898;179594897;179594896
N2AB	5760	17503;17504;17505	chr2:178730171;178730170;178730169	chr2:179594898;179594897;179594896
N2A	4833	14722;14723;14724	chr2:178730171;178730170;178730169	chr2:179594898;179594897;179594896
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: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-44
• Domain position: 66
• Structural Position: 148
• Q(SASA): 0.6227
• 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
T/N	rs773941728	0.273	0.055	N	0.199	0.108	0.16115917748	gnomAD-2.1.1	8.06E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
T/N	rs773941728	0.273	0.055	N	0.199	0.108	0.16115917748	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	4.41E-05	0	0
T/N	rs773941728	0.273	0.055	N	0.199	0.108	0.16115917748	gnomAD-4.0.0	2.29344E-05	None	None	None	None	N	None	1.33533E-05	0	None	0	0	None	0	0	3.05173E-05	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
T/A	0.0549	likely_benign	0.053	benign	-0.231	Destabilizing	None	N	0.075	neutral	N	0.435601128	None	None	N
T/C	0.3539	ambiguous	0.3341	benign	-0.206	Destabilizing	0.356	N	0.257	neutral	None	None	None	None	N
T/D	0.1936	likely_benign	0.1741	benign	0.116	Stabilizing	0.072	N	0.302	neutral	None	None	None	None	N
T/E	0.1771	likely_benign	0.1607	benign	0.021	Stabilizing	0.072	N	0.28	neutral	None	None	None	None	N
T/F	0.17	likely_benign	0.1666	benign	-0.867	Destabilizing	0.214	N	0.298	neutral	None	None	None	None	N
T/G	0.1041	likely_benign	0.1012	benign	-0.304	Destabilizing	0.016	N	0.256	neutral	None	None	None	None	N
T/H	0.1984	likely_benign	0.1852	benign	-0.554	Destabilizing	0.628	D	0.242	neutral	None	None	None	None	N
T/I	0.1212	likely_benign	0.1152	benign	-0.163	Destabilizing	0.01	N	0.281	neutral	N	0.454540025	None	None	N
T/K	0.159	likely_benign	0.1439	benign	-0.223	Destabilizing	0.072	N	0.286	neutral	None	None	None	None	N
T/L	0.0807	likely_benign	0.0805	benign	-0.163	Destabilizing	0.016	N	0.276	neutral	None	None	None	None	N
T/M	0.0827	likely_benign	0.0835	benign	-0.002	Destabilizing	0.214	N	0.251	neutral	None	None	None	None	N
T/N	0.0807	likely_benign	0.0797	benign	0.008	Stabilizing	0.055	N	0.199	neutral	N	0.456515118	None	None	N
T/P	0.1026	likely_benign	0.1027	benign	-0.161	Destabilizing	0.055	N	0.341	neutral	N	0.486011306	None	None	N
T/Q	0.1649	likely_benign	0.1538	benign	-0.237	Destabilizing	0.356	N	0.326	neutral	None	None	None	None	N
T/R	0.1331	likely_benign	0.1243	benign	0.056	Stabilizing	0.072	N	0.318	neutral	None	None	None	None	N
T/S	0.0681	likely_benign	0.0674	benign	-0.179	Destabilizing	None	N	0.097	neutral	N	0.357388274	None	None	N
T/V	0.0987	likely_benign	0.0953	benign	-0.161	Destabilizing	None	N	0.093	neutral	None	None	None	None	N
T/W	0.3944	ambiguous	0.3842	ambiguous	-0.915	Destabilizing	0.864	D	0.257	neutral	None	None	None	None	N
T/Y	0.2023	likely_benign	0.1993	benign	-0.605	Destabilizing	0.356	N	0.262	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.