TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27330	82213;82214;82215	chr2:178564144;178564143;178564142	chr2:179428871;179428870;179428869
N2AB	25689	77290;77291;77292	chr2:178564144;178564143;178564142	chr2:179428871;179428870;179428869
N2A	24762	74509;74510;74511	chr2:178564144;178564143;178564142	chr2:179428871;179428870;179428869
N2B	18265	55018;55019;55020	chr2:178564144;178564143;178564142	chr2:179428871;179428870;179428869
Novex-1	18390	55393;55394;55395	chr2:178564144;178564143;178564142	chr2:179428871;179428870;179428869
Novex-2	18457	55594;55595;55596	chr2:178564144;178564143;178564142	chr2:179428871;179428870;179428869
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAG
• RefSeq wild type template codon: GTC
• Domain: Ig-140
• Domain position: 53
• Structural Position: 134
• Q(SASA): 0.4721
• 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
Q/E	rs1205501595	0.075	0.005	N	0.116	0.166	0.273070737957	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
Q/E	rs1205501595	0.075	0.005	N	0.116	0.166	0.273070737957	gnomAD-4.0.0	1.5913E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43275E-05	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	0.2112	likely_benign	0.2127	benign	-0.181	Destabilizing	0.688	D	0.341	neutral	None	None	None	None	N
Q/C	0.5913	likely_pathogenic	0.5869	pathogenic	0.119	Stabilizing	0.998	D	0.491	neutral	None	None	None	None	N
Q/D	0.2591	likely_benign	0.2515	benign	0.206	Stabilizing	0.525	D	0.256	neutral	None	None	None	None	N
Q/E	0.07	likely_benign	0.07	benign	0.206	Stabilizing	0.005	N	0.116	neutral	N	0.411037197	None	None	N
Q/F	0.5965	likely_pathogenic	0.597	pathogenic	-0.271	Destabilizing	0.991	D	0.507	neutral	None	None	None	None	N
Q/G	0.1839	likely_benign	0.1837	benign	-0.4	Destabilizing	0.915	D	0.408	neutral	None	None	None	None	N
Q/H	0.1974	likely_benign	0.1825	benign	-0.185	Destabilizing	0.966	D	0.41	neutral	N	0.454425402	None	None	N
Q/I	0.4489	ambiguous	0.4447	ambiguous	0.314	Stabilizing	0.949	D	0.481	neutral	None	None	None	None	N
Q/K	0.1209	likely_benign	0.1085	benign	0.055	Stabilizing	0.454	N	0.275	neutral	N	0.382754518	None	None	N
Q/L	0.1359	likely_benign	0.1367	benign	0.314	Stabilizing	0.801	D	0.408	neutral	N	0.443208331	None	None	N
Q/M	0.3613	ambiguous	0.3624	ambiguous	0.398	Stabilizing	0.991	D	0.418	neutral	None	None	None	None	N
Q/N	0.2316	likely_benign	0.2307	benign	-0.339	Destabilizing	0.842	D	0.279	neutral	None	None	None	None	N
Q/P	0.2515	likely_benign	0.2372	benign	0.179	Stabilizing	0.891	D	0.402	neutral	N	0.465373115	None	None	N
Q/R	0.1101	likely_benign	0.1046	benign	0.192	Stabilizing	0.801	D	0.297	neutral	N	0.421139548	None	None	N
Q/S	0.2023	likely_benign	0.2056	benign	-0.355	Destabilizing	0.525	D	0.279	neutral	None	None	None	None	N
Q/T	0.178	likely_benign	0.1736	benign	-0.19	Destabilizing	0.029	N	0.166	neutral	None	None	None	None	N
Q/V	0.2898	likely_benign	0.2877	benign	0.179	Stabilizing	0.842	D	0.406	neutral	None	None	None	None	N
Q/W	0.4359	ambiguous	0.4083	ambiguous	-0.257	Destabilizing	0.998	D	0.497	neutral	None	None	None	None	N
Q/Y	0.3669	ambiguous	0.3629	ambiguous	-0.002	Destabilizing	0.991	D	0.441	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.