TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6999	21220;21221;21222	chr2:178724380;178724379;178724378	chr2:179589107;179589106;179589105
N2AB	6682	20269;20270;20271	chr2:178724380;178724379;178724378	chr2:179589107;179589106;179589105
N2A	5755	17488;17489;17490	chr2:178724380;178724379;178724378	chr2:179589107;179589106;179589105
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: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-54
• Domain position: 52
• Structural Position: 130
• Q(SASA): 0.4946
• 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
Y/C	rs1343770232	-0.286	0.56	D	0.215	0.236	0.442466506703	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
Y/C	rs1343770232	-0.286	0.56	D	0.215	0.236	0.442466506703	gnomAD-4.0.0	6.84326E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	1.73671E-04	8.09636E-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
Y/A	0.266	likely_benign	0.2671	benign	-0.492	Destabilizing	0.007	N	0.283	neutral	None	None	None	None	N
Y/C	0.0876	likely_benign	0.0918	benign	0.033	Stabilizing	0.56	D	0.215	neutral	D	0.526381501	None	None	N
Y/D	0.16	likely_benign	0.1664	benign	0.823	Stabilizing	0.029	N	0.307	neutral	N	0.409284971	None	None	N
Y/E	0.3873	ambiguous	0.3863	ambiguous	0.806	Stabilizing	0.001	N	0.208	neutral	None	None	None	None	N
Y/F	0.0765	likely_benign	0.0794	benign	-0.221	Destabilizing	None	N	0.173	neutral	N	0.456982918	None	None	N
Y/G	0.2724	likely_benign	0.2738	benign	-0.654	Destabilizing	0.031	N	0.276	neutral	None	None	None	None	N
Y/H	0.0952	likely_benign	0.0959	benign	0.319	Stabilizing	None	N	0.144	neutral	N	0.446573923	None	None	N
Y/I	0.1948	likely_benign	0.2023	benign	-0.095	Destabilizing	0.016	N	0.25	neutral	None	None	None	None	N
Y/K	0.3488	ambiguous	0.3517	ambiguous	0.163	Stabilizing	0.072	N	0.298	neutral	None	None	None	None	N
Y/L	0.2222	likely_benign	0.2189	benign	-0.095	Destabilizing	None	N	0.139	neutral	None	None	None	None	N
Y/M	0.3759	ambiguous	0.3935	ambiguous	-0.144	Destabilizing	0.214	N	0.221	neutral	None	None	None	None	N
Y/N	0.1018	likely_benign	0.1049	benign	-0.131	Destabilizing	0.055	N	0.311	neutral	N	0.436663574	None	None	N
Y/P	0.7688	likely_pathogenic	0.7393	pathogenic	-0.209	Destabilizing	0.136	N	0.319	neutral	None	None	None	None	N
Y/Q	0.2181	likely_benign	0.2151	benign	-0.032	Destabilizing	0.072	N	0.303	neutral	None	None	None	None	N
Y/R	0.2165	likely_benign	0.2143	benign	0.322	Stabilizing	0.072	N	0.337	neutral	None	None	None	None	N
Y/S	0.0942	likely_benign	0.1011	benign	-0.478	Destabilizing	0.002	N	0.21	neutral	N	0.415749584	None	None	N
Y/T	0.2042	likely_benign	0.2191	benign	-0.409	Destabilizing	None	N	0.146	neutral	None	None	None	None	N
Y/V	0.1695	likely_benign	0.1735	benign	-0.209	Destabilizing	None	N	0.158	neutral	None	None	None	None	N
Y/W	0.3225	likely_benign	0.3235	benign	-0.406	Destabilizing	0.356	N	0.295	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.