TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18755	56488;56489;56490	chr2:178599638;178599637;178599636	chr2:179464365;179464364;179464363
N2AB	17114	51565;51566;51567	chr2:178599638;178599637;178599636	chr2:179464365;179464364;179464363
N2A	16187	48784;48785;48786	chr2:178599638;178599637;178599636	chr2:179464365;179464364;179464363
N2B	9690	29293;29294;29295	chr2:178599638;178599637;178599636	chr2:179464365;179464364;179464363
Novex-1	9815	29668;29669;29670	chr2:178599638;178599637;178599636	chr2:179464365;179464364;179464363
Novex-2	9882	29869;29870;29871	chr2:178599638;178599637;178599636	chr2:179464365;179464364;179464363
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGC
• RefSeq wild type template codon: GCG
• Domain: Ig-116
• Domain position: 68
• Structural Position: 145
• Q(SASA): 0.6475
• 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
R/C	rs143659933	-0.452	0.173	N	0.351	0.237	None	gnomAD-2.1.1	4.3E-05	None	None	None	None	N	None	4.14E-05	5.68E-05	None	0	5.15E-05	None	3.28E-05	None	0	5.49E-05	0
R/C	rs143659933	-0.452	0.173	N	0.351	0.237	None	gnomAD-3.1.2	3.95E-05	None	None	None	None	N	None	4.83E-05	0	0	0	3.88048E-04	None	0	0	2.94E-05	0	0
R/C	rs143659933	-0.452	0.173	N	0.351	0.237	None	gnomAD-4.0.0	1.79829E-05	None	None	None	None	N	None	2.66873E-05	3.33712E-05	None	0	4.46688E-05	None	0	0	1.61123E-05	0	6.40718E-05
R/H	rs772767570	-1.173	0.995	N	0.407	0.259	0.310458034454	gnomAD-2.1.1	1.62E-05	None	None	None	None	N	None	1.29534E-04	0	None	0	5.59E-05	None	0	None	0	8.92E-06	0
R/H	rs772767570	-1.173	0.995	N	0.407	0.259	0.310458034454	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
R/H	rs772767570	-1.173	0.995	N	0.407	0.259	0.310458034454	gnomAD-4.0.0	6.82281E-06	None	None	None	None	N	None	5.34645E-05	0	None	0	2.23214E-05	None	0	0	1.69625E-06	4.40529E-05	0
R/L	rs772767570	None	0.929	N	0.363	0.317	0.48461828368	gnomAD-4.0.0	6.84819E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00001E-07	0	0
R/S	rs143659933	-0.528	0.336	N	0.183	0.238	0.26547132957	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	5.59E-05	None	0	None	0	0	0
R/S	rs143659933	-0.528	0.336	N	0.183	0.238	0.26547132957	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	1.94024E-04	None	0	0	0	0	0
R/S	rs143659933	-0.528	0.336	N	0.183	0.238	0.26547132957	gnomAD-4.0.0	6.5741E-06	None	None	None	None	N	None	0	0	None	0	1.94477E-04	None	0	0	0	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
R/A	0.2766	likely_benign	0.2707	benign	-0.36	Destabilizing	0.584	D	0.371	neutral	None	None	None	None	N
R/C	0.1125	likely_benign	0.1166	benign	-0.156	Destabilizing	0.173	N	0.351	neutral	N	0.469952215	None	None	N
R/D	0.4915	ambiguous	0.4906	ambiguous	0.052	Stabilizing	0.872	D	0.374	neutral	None	None	None	None	N
R/E	0.2365	likely_benign	0.2448	benign	0.158	Stabilizing	0.584	D	0.331	neutral	None	None	None	None	N
R/F	0.3918	ambiguous	0.3783	ambiguous	-0.308	Destabilizing	0.993	D	0.355	neutral	None	None	None	None	N
R/G	0.162	likely_benign	0.1693	benign	-0.652	Destabilizing	0.843	D	0.361	neutral	N	0.470066858	None	None	N
R/H	0.0832	likely_benign	0.0873	benign	-1.178	Destabilizing	0.995	D	0.407	neutral	N	0.48091857	None	None	N
R/I	0.1816	likely_benign	0.1785	benign	0.408	Stabilizing	0.98	D	0.363	neutral	None	None	None	None	N
R/K	0.0696	likely_benign	0.0739	benign	-0.334	Destabilizing	0.037	N	0.176	neutral	None	None	None	None	N
R/L	0.1676	likely_benign	0.1656	benign	0.408	Stabilizing	0.929	D	0.363	neutral	N	0.468354705	None	None	N
R/M	0.1852	likely_benign	0.183	benign	0.092	Stabilizing	0.993	D	0.378	neutral	None	None	None	None	N
R/N	0.3506	ambiguous	0.352	ambiguous	0.195	Stabilizing	0.872	D	0.306	neutral	None	None	None	None	N
R/P	0.8147	likely_pathogenic	0.797	pathogenic	0.174	Stabilizing	0.989	D	0.364	neutral	N	0.495772095	None	None	N
R/Q	0.0776	likely_benign	0.0802	benign	0.042	Stabilizing	0.209	N	0.235	neutral	None	None	None	None	N
R/S	0.2813	likely_benign	0.2799	benign	-0.403	Destabilizing	0.336	N	0.183	neutral	N	0.441821464	None	None	N
R/T	0.1393	likely_benign	0.1419	benign	-0.126	Destabilizing	0.773	D	0.357	neutral	None	None	None	None	N
R/V	0.2243	likely_benign	0.2178	benign	0.174	Stabilizing	0.872	D	0.39	neutral	None	None	None	None	N
R/W	0.1754	likely_benign	0.1776	benign	-0.117	Destabilizing	0.998	D	0.367	neutral	None	None	None	None	N
R/Y	0.3132	likely_benign	0.3126	benign	0.224	Stabilizing	0.993	D	0.355	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.