TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15348	46267;46268;46269	chr2:178620479;178620478;178620477	chr2:179485206;179485205;179485204
N2AB	13707	41344;41345;41346	chr2:178620479;178620478;178620477	chr2:179485206;179485205;179485204
N2A	12780	38563;38564;38565	chr2:178620479;178620478;178620477	chr2:179485206;179485205;179485204
N2B	6283	19072;19073;19074	chr2:178620479;178620478;178620477	chr2:179485206;179485205;179485204
Novex-1	6408	19447;19448;19449	chr2:178620479;178620478;178620477	chr2:179485206;179485205;179485204
Novex-2	6475	19648;19649;19650	chr2:178620479;178620478;178620477	chr2:179485206;179485205;179485204
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Ig-105
• Domain position: 47
• Structural Position: 122
• Q(SASA): 0.3313
• 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
S/A	rs766291551	-0.709	0.001	N	0.256	0.082	0.0846915920261	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.95E-06	0
S/A	rs766291551	-0.709	0.001	N	0.256	0.082	0.0846915920261	gnomAD-4.0.0	1.59412E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.0303E-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
S/A	0.0882	likely_benign	0.103	benign	-0.874	Destabilizing	0.001	N	0.256	neutral	N	0.466653008	None	None	N
S/C	0.1044	likely_benign	0.1319	benign	-0.665	Destabilizing	0.245	N	0.365	neutral	None	None	None	None	N
S/D	0.3921	ambiguous	0.4645	ambiguous	-0.792	Destabilizing	0.044	N	0.307	neutral	None	None	None	None	N
S/E	0.3613	ambiguous	0.4611	ambiguous	-0.697	Destabilizing	0.009	N	0.277	neutral	None	None	None	None	N
S/F	0.1362	likely_benign	0.1685	benign	-0.917	Destabilizing	0.022	N	0.483	neutral	None	None	None	None	N
S/G	0.1359	likely_benign	0.1642	benign	-1.204	Destabilizing	0.018	N	0.297	neutral	None	None	None	None	N
S/H	0.1933	likely_benign	0.2342	benign	-1.671	Destabilizing	0.245	N	0.366	neutral	None	None	None	None	N
S/I	0.0979	likely_benign	0.1234	benign	-0.076	Destabilizing	None	N	0.189	neutral	None	None	None	None	N
S/K	0.4079	ambiguous	0.5067	ambiguous	-0.521	Destabilizing	0.009	N	0.277	neutral	None	None	None	None	N
S/L	0.0802	likely_benign	0.0978	benign	-0.076	Destabilizing	None	N	0.155	neutral	N	0.375998722	None	None	N
S/M	0.1359	likely_benign	0.1803	benign	0.059	Stabilizing	0.074	N	0.45	neutral	None	None	None	None	N
S/N	0.1293	likely_benign	0.1607	benign	-0.838	Destabilizing	0.044	N	0.336	neutral	None	None	None	None	N
S/P	0.7931	likely_pathogenic	0.8711	pathogenic	-0.307	Destabilizing	0.065	N	0.419	neutral	N	0.503273754	None	None	N
S/Q	0.2769	likely_benign	0.3649	ambiguous	-0.82	Destabilizing	0.002	N	0.164	neutral	None	None	None	None	N
S/R	0.3519	ambiguous	0.4282	ambiguous	-0.671	Destabilizing	0.044	N	0.413	neutral	None	None	None	None	N
S/T	0.0708	likely_benign	0.0914	benign	-0.7	Destabilizing	None	N	0.121	neutral	N	0.467074638	None	None	N
S/V	0.109	likely_benign	0.1476	benign	-0.307	Destabilizing	None	N	0.162	neutral	None	None	None	None	N
S/W	0.2242	likely_benign	0.2695	benign	-0.989	Destabilizing	0.788	D	0.451	neutral	None	None	None	None	N
S/Y	0.1391	likely_benign	0.1592	benign	-0.638	Destabilizing	0.085	N	0.499	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.