TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17193	51802;51803;51804	chr2:178609846;178609845;178609844	chr2:179474573;179474572;179474571
N2AB	15552	46879;46880;46881	chr2:178609846;178609845;178609844	chr2:179474573;179474572;179474571
N2A	14625	44098;44099;44100	chr2:178609846;178609845;178609844	chr2:179474573;179474572;179474571
N2B	8128	24607;24608;24609	chr2:178609846;178609845;178609844	chr2:179474573;179474572;179474571
Novex-1	8253	24982;24983;24984	chr2:178609846;178609845;178609844	chr2:179474573;179474572;179474571
Novex-2	8320	25183;25184;25185	chr2:178609846;178609845;178609844	chr2:179474573;179474572;179474571
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGG
• RefSeq wild type template codon: TCC
• Domain: Fn3-13
• Domain position: 47
• Structural Position: 64
• Q(SASA): 0.6072
• 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/S	rs759285989	-0.009	0.012	N	0.365	0.093	0.0482279557977	gnomAD-2.1.1	1.61E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	3.56E-05	0
R/S	rs759285989	-0.009	0.012	N	0.365	0.093	0.0482279557977	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
R/S	rs759285989	-0.009	0.012	N	0.365	0.093	0.0482279557977	gnomAD-4.0.0	9.92025E-06	None	None	None	None	N	None	2.67401E-05	0	None	0	0	None	0	3.29164E-04	7.63175E-06	1.0983E-05	3.20472E-05

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	0.2238	likely_benign	0.2383	benign	0.071	Stabilizing	0.016	N	0.383	neutral	None	None	None	None	N
R/C	0.1969	likely_benign	0.1923	benign	-0.287	Destabilizing	0.676	D	0.298	neutral	None	None	None	None	N
R/D	0.3923	ambiguous	0.4268	ambiguous	-0.353	Destabilizing	0.038	N	0.371	neutral	None	None	None	None	N
R/E	0.2041	likely_benign	0.2275	benign	-0.303	Destabilizing	0.016	N	0.319	neutral	None	None	None	None	N
R/F	0.406	ambiguous	0.4086	ambiguous	-0.22	Destabilizing	0.356	N	0.307	neutral	None	None	None	None	N
R/G	0.16	likely_benign	0.175	benign	-0.079	Destabilizing	0.024	N	0.321	neutral	N	0.460123932	None	None	N
R/H	0.0972	likely_benign	0.0981	benign	-0.57	Destabilizing	0.356	N	0.281	neutral	None	None	None	None	N
R/I	0.1646	likely_benign	0.1711	benign	0.423	Stabilizing	0.12	N	0.354	neutral	None	None	None	None	N
R/K	0.0688	likely_benign	0.0668	benign	-0.18	Destabilizing	None	N	0.111	neutral	N	0.445559911	None	None	N
R/L	0.1869	likely_benign	0.1974	benign	0.423	Stabilizing	0.038	N	0.339	neutral	None	None	None	None	N
R/M	0.1709	likely_benign	0.1774	benign	-0.092	Destabilizing	0.295	N	0.31	neutral	D	0.523695407	None	None	N
R/N	0.241	likely_benign	0.256	benign	-0.145	Destabilizing	0.001	N	0.238	neutral	None	None	None	None	N
R/P	0.6566	likely_pathogenic	0.6698	pathogenic	0.324	Stabilizing	0.356	N	0.353	neutral	None	None	None	None	N
R/Q	0.0839	likely_benign	0.0866	benign	-0.157	Destabilizing	0.038	N	0.304	neutral	None	None	None	None	N
R/S	0.2537	likely_benign	0.2695	benign	-0.296	Destabilizing	0.012	N	0.365	neutral	N	0.465625752	None	None	N
R/T	0.1211	likely_benign	0.1279	benign	-0.136	Destabilizing	None	N	0.245	neutral	N	0.442751679	None	None	N
R/V	0.1984	likely_benign	0.2056	benign	0.324	Stabilizing	0.038	N	0.361	neutral	None	None	None	None	N
R/W	0.238	likely_benign	0.2435	benign	-0.406	Destabilizing	0.828	D	0.323	neutral	N	0.494588374	None	None	N
R/Y	0.3171	likely_benign	0.314	benign	0.002	Stabilizing	0.356	N	0.321	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.