TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17335	52228;52229;52230	chr2:178609307;178609306;178609305	chr2:179474034;179474033;179474032
N2AB	15694	47305;47306;47307	chr2:178609307;178609306;178609305	chr2:179474034;179474033;179474032
N2A	14767	44524;44525;44526	chr2:178609307;178609306;178609305	chr2:179474034;179474033;179474032
N2B	8270	25033;25034;25035	chr2:178609307;178609306;178609305	chr2:179474034;179474033;179474032
Novex-1	8395	25408;25409;25410	chr2:178609307;178609306;178609305	chr2:179474034;179474033;179474032
Novex-2	8462	25609;25610;25611	chr2:178609307;178609306;178609305	chr2:179474034;179474033;179474032
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-112
• Domain position: 85
• Structural Position: 139
• Q(SASA): 0.2543
• 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	rs763755830	-1.859	0.002	N	0.571	0.178	None	gnomAD-2.1.1	1.46E-05	None	None	None	None	N	None	0	0	None	0	5.23E-05	None	0	None	4.07E-05	1.59E-05	0
R/C	rs763755830	-1.859	0.002	N	0.571	0.178	None	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	2.94E-05	0	0
R/C	rs763755830	-1.859	0.002	N	0.571	0.178	None	gnomAD-4.0.0	1.30764E-05	None	None	None	None	N	None	1.34351E-05	0	None	0	2.24558E-05	None	1.56902E-05	0	1.36057E-05	2.22489E-05	0
R/G	None	None	None	N	0.398	0.236	0.490771696789	gnomAD-4.0.0	6.87758E-07	None	None	None	None	N	None	0	0	None	0	2.53846E-05	None	0	0	0	0	0
R/H	rs367603302	-2.017	0.006	N	0.339	0.129	None	gnomAD-2.1.1	1.31519E-04	None	None	None	None	N	None	4.98587E-04	1.15788E-04	None	1.11449E-03	0	None	3.42E-05	None	0	3.19E-05	5.74878E-04
R/H	rs367603302	-2.017	0.006	N	0.339	0.129	None	gnomAD-3.1.2	1.71143E-04	None	None	None	None	N	None	4.83045E-04	0	0	8.65052E-04	0	None	0	0	4.42E-05	0	0
R/H	rs367603302	-2.017	0.006	N	0.339	0.129	None	gnomAD-4.0.0	8.65936E-05	None	None	None	None	N	None	3.89607E-04	8.45881E-05	None	1.09837E-03	0	None	0	3.31126E-04	5.35884E-05	2.2303E-05	9.66526E-05
R/L	rs367603302	None	None	N	0.408	0.224	0.497613835824	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.42E-05	0	0	0	0	None	0	0	0	0	0
R/L	rs367603302	None	None	N	0.408	0.224	0.497613835824	gnomAD-4.0.0	6.58241E-06	None	None	None	None	N	None	2.41523E-05	0	None	0	0	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	0.3567	ambiguous	0.2895	benign	-1.263	Destabilizing	None	N	0.286	neutral	None	None	None	None	N
R/C	0.1302	likely_benign	0.1171	benign	-1.473	Destabilizing	0.002	N	0.571	neutral	N	0.486381254	None	None	N
R/D	0.7424	likely_pathogenic	0.6839	pathogenic	-0.699	Destabilizing	0.148	N	0.579	neutral	None	None	None	None	N
R/E	0.3993	ambiguous	0.3562	ambiguous	-0.558	Destabilizing	0.148	N	0.473	neutral	None	None	None	None	N
R/F	0.3236	likely_benign	0.2649	benign	-1.058	Destabilizing	0.001	N	0.585	neutral	None	None	None	None	N
R/G	0.3682	ambiguous	0.3172	benign	-1.578	Destabilizing	None	N	0.398	neutral	N	0.485874275	None	None	N
R/H	0.0822	likely_benign	0.0796	benign	-1.585	Destabilizing	0.006	N	0.339	neutral	N	0.509145321	None	None	N
R/I	0.1351	likely_benign	0.1109	benign	-0.398	Destabilizing	0.08	N	0.469	neutral	None	None	None	None	N
R/K	0.1016	likely_benign	0.0988	benign	-1.412	Destabilizing	0.07	N	0.409	neutral	None	None	None	None	N
R/L	0.1622	likely_benign	0.138	benign	-0.398	Destabilizing	None	N	0.408	neutral	N	0.483766874	None	None	N
R/M	0.1826	likely_benign	0.1472	benign	-0.711	Destabilizing	0.596	D	0.615	neutral	None	None	None	None	N
R/N	0.5428	ambiguous	0.4869	ambiguous	-1.004	Destabilizing	0.08	N	0.564	neutral	None	None	None	None	N
R/P	0.9583	likely_pathogenic	0.948	pathogenic	-0.668	Destabilizing	0.62	D	0.621	neutral	N	0.497648654	None	None	N
R/Q	0.1143	likely_benign	0.1114	benign	-1.125	Destabilizing	0.296	N	0.573	neutral	None	None	None	None	N
R/S	0.4121	ambiguous	0.3514	ambiguous	-1.798	Destabilizing	0.002	N	0.293	neutral	N	0.480438568	None	None	N
R/T	0.1712	likely_benign	0.1417	benign	-1.474	Destabilizing	0.036	N	0.397	neutral	None	None	None	None	N
R/V	0.1989	likely_benign	0.165	benign	-0.668	Destabilizing	0.002	N	0.569	neutral	None	None	None	None	N
R/W	0.1259	likely_benign	0.1066	benign	-0.666	Destabilizing	0.901	D	0.639	neutral	None	None	None	None	N
R/Y	0.2792	likely_benign	0.2455	benign	-0.362	Destabilizing	0.174	N	0.62	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.