TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16456	49591;49592;49593	chr2:178613917;178613916;178613915	chr2:179478644;179478643;179478642
N2AB	14815	44668;44669;44670	chr2:178613917;178613916;178613915	chr2:179478644;179478643;179478642
N2A	13888	41887;41888;41889	chr2:178613917;178613916;178613915	chr2:179478644;179478643;179478642
N2B	7391	22396;22397;22398	chr2:178613917;178613916;178613915	chr2:179478644;179478643;179478642
Novex-1	7516	22771;22772;22773	chr2:178613917;178613916;178613915	chr2:179478644;179478643;179478642
Novex-2	7583	22972;22973;22974	chr2:178613917;178613916;178613915	chr2:179478644;179478643;179478642
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: Fn3-7
• Domain position: 7
• Structural Position: 7
• Q(SASA): 0.7437
• 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	rs727504986	0.097	0.996	N	0.339	0.344	0.565096191312	gnomAD-2.1.1	1.09E-05	None	None	None	None	N	None	4.15E-05	0	None	0	1.03896E-04	None	0	None	0	0	0
R/C	rs727504986	0.097	0.996	N	0.339	0.344	0.565096191312	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	2.42E-05	0	0	0	3.90168E-04	None	0	0	0	0	0
R/C	rs727504986	0.097	0.996	N	0.339	0.344	0.565096191312	gnomAD-4.0.0	9.32791E-06	None	None	None	None	N	None	4.02361E-05	1.68606E-05	None	0	1.11862E-04	None	0	0	4.24812E-06	1.10924E-05	0
R/H	rs768914789	-0.636	0.956	N	0.478	0.131	None	gnomAD-2.1.1	5.45E-05	None	None	None	None	N	None	1.66003E-04	2.9E-05	None	0	1.55699E-04	None	1.7052E-04	None	0	1.58E-05	0
R/H	rs768914789	-0.636	0.956	N	0.478	0.131	None	gnomAD-3.1.2	5.27E-05	None	None	None	None	N	None	1.69213E-04	0	0	0	0	None	0	0	0	2.07727E-04	0
R/H	rs768914789	-0.636	0.956	N	0.478	0.131	None	gnomAD-4.0.0	3.04784E-05	None	None	None	None	N	None	1.74352E-04	1.68754E-05	None	0	1.78995E-04	None	0	0	1.52946E-05	8.88533E-05	1.60829E-05
R/L	rs768914789	0.579	0.579	N	0.46	0.211	0.454426139905	gnomAD-2.1.1	8.2E-06	None	None	None	None	N	None	6.5E-05	0	None	0	0	None	0	None	0	9.02E-06	0
R/L	rs768914789	0.579	0.579	N	0.46	0.211	0.454426139905	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	2.42E-05	0	0	0	0	None	0	0	1.47E-05	0	0
R/L	rs768914789	0.579	0.579	N	0.46	0.211	0.454426139905	gnomAD-4.0.0	3.11004E-06	None	None	None	None	N	None	1.34117E-05	0	None	0	0	None	0	0	3.39881E-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
R/A	0.3757	ambiguous	0.372	ambiguous	-0.048	Destabilizing	0.129	N	0.405	neutral	None	None	None	None	N
R/C	0.1952	likely_benign	0.2122	benign	-0.072	Destabilizing	0.996	D	0.339	neutral	N	0.483990372	None	None	N
R/D	0.5318	ambiguous	0.5218	ambiguous	-0.147	Destabilizing	0.264	N	0.42	neutral	None	None	None	None	N
R/E	0.4111	ambiguous	0.4088	ambiguous	-0.095	Destabilizing	0.129	N	0.391	neutral	None	None	None	None	N
R/F	0.5925	likely_pathogenic	0.5899	pathogenic	-0.278	Destabilizing	0.94	D	0.364	neutral	None	None	None	None	N
R/G	0.2748	likely_benign	0.2779	benign	-0.236	Destabilizing	0.002	N	0.221	neutral	N	0.457904476	None	None	N
R/H	0.1177	likely_benign	0.1196	benign	-0.71	Destabilizing	0.956	D	0.478	neutral	N	0.480126209	None	None	N
R/I	0.369	ambiguous	0.3696	ambiguous	0.411	Stabilizing	0.836	D	0.391	neutral	None	None	None	None	N
R/K	0.1219	likely_benign	0.1166	benign	-0.082	Destabilizing	0.001	N	0.171	neutral	None	None	None	None	N
R/L	0.3049	likely_benign	0.298	benign	0.411	Stabilizing	0.579	D	0.46	neutral	N	0.477589604	None	None	N
R/M	0.3134	likely_benign	0.3254	benign	0.092	Stabilizing	0.94	D	0.419	neutral	None	None	None	None	N
R/N	0.3879	ambiguous	0.4253	ambiguous	0.243	Stabilizing	0.001	N	0.188	neutral	None	None	None	None	N
R/P	0.8712	likely_pathogenic	0.8088	pathogenic	0.278	Stabilizing	0.907	D	0.423	neutral	N	0.466032652	None	None	N
R/Q	0.1179	likely_benign	0.1217	benign	0.088	Stabilizing	0.264	N	0.482	neutral	None	None	None	None	N
R/S	0.4052	ambiguous	0.4107	ambiguous	-0.117	Destabilizing	0.221	N	0.383	neutral	N	0.464115434	None	None	N
R/T	0.2814	likely_benign	0.2691	benign	0.06	Stabilizing	0.418	N	0.429	neutral	None	None	None	None	N
R/V	0.4016	ambiguous	0.3863	ambiguous	0.278	Stabilizing	0.418	N	0.446	neutral	None	None	None	None	N
R/W	0.3052	likely_benign	0.2918	benign	-0.313	Destabilizing	0.983	D	0.391	neutral	None	None	None	None	N
R/Y	0.4087	ambiguous	0.4111	ambiguous	0.085	Stabilizing	0.94	D	0.395	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.