TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7790	23593;23594;23595	chr2:178720394;178720393;178720392	chr2:179585121;179585120;179585119
N2AB	7473	22642;22643;22644	chr2:178720394;178720393;178720392	chr2:179585121;179585120;179585119
N2A	6546	19861;19862;19863	chr2:178720394;178720393;178720392	chr2:179585121;179585120;179585119
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: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-62
• Domain position: 89
• Structural Position: 175
• Q(SASA): 0.555
• 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
K/N	rs752463765	0.003	0.016	D	0.267	0.124	0.117506650769	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.32E-05	None	0	0	0
K/N	rs752463765	0.003	0.016	D	0.267	0.124	0.117506650769	gnomAD-4.0.0	1.59836E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.443E-05	0
K/T	rs756098759	-0.24	0.379	N	0.404	0.308	0.273938319068	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.94E-06	0
K/T	rs756098759	-0.24	0.379	N	0.404	0.308	0.273938319068	gnomAD-4.0.0	1.59754E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86891E-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
K/A	0.2243	likely_benign	0.2715	benign	-0.192	Destabilizing	0.25	N	0.397	neutral	None	None	None	None	N
K/C	0.553	ambiguous	0.621	pathogenic	-0.452	Destabilizing	0.992	D	0.505	neutral	None	None	None	None	N
K/D	0.4661	ambiguous	0.5365	ambiguous	0.413	Stabilizing	0.447	N	0.411	neutral	None	None	None	None	N
K/E	0.1469	likely_benign	0.1811	benign	0.466	Stabilizing	0.016	N	0.233	neutral	N	0.499426973	None	None	N
K/F	0.5185	ambiguous	0.5777	pathogenic	-0.21	Destabilizing	0.972	D	0.473	neutral	None	None	None	None	N
K/G	0.3798	ambiguous	0.4556	ambiguous	-0.455	Destabilizing	0.617	D	0.447	neutral	None	None	None	None	N
K/H	0.1912	likely_benign	0.2145	benign	-0.707	Destabilizing	0.92	D	0.43	neutral	None	None	None	None	N
K/I	0.1868	likely_benign	0.215	benign	0.439	Stabilizing	0.92	D	0.489	neutral	None	None	None	None	N
K/L	0.2078	likely_benign	0.2477	benign	0.439	Stabilizing	0.617	D	0.44	neutral	None	None	None	None	N
K/M	0.1495	likely_benign	0.1745	benign	0.182	Stabilizing	0.97	D	0.415	neutral	N	0.510815385	None	None	N
K/N	0.2632	likely_benign	0.3145	benign	0.026	Stabilizing	0.016	N	0.267	neutral	D	0.522458548	None	None	N
K/P	0.7819	likely_pathogenic	0.8451	pathogenic	0.259	Stabilizing	0.92	D	0.432	neutral	None	None	None	None	N
K/Q	0.0902	likely_benign	0.102	benign	-0.092	Destabilizing	0.036	N	0.261	neutral	N	0.510027969	None	None	N
K/R	0.0761	likely_benign	0.0779	benign	-0.149	Destabilizing	0.004	N	0.297	neutral	N	0.492098356	None	None	N
K/S	0.2335	likely_benign	0.2857	benign	-0.617	Destabilizing	0.059	N	0.255	neutral	None	None	None	None	N
K/T	0.0891	likely_benign	0.105	benign	-0.382	Destabilizing	0.379	N	0.404	neutral	N	0.428161521	None	None	N
K/V	0.1854	likely_benign	0.2142	benign	0.259	Stabilizing	0.85	D	0.418	neutral	None	None	None	None	N
K/W	0.6075	likely_pathogenic	0.6568	pathogenic	-0.136	Destabilizing	0.992	D	0.596	neutral	None	None	None	None	N
K/Y	0.4186	ambiguous	0.4616	ambiguous	0.2	Stabilizing	0.972	D	0.454	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.