TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8793	26602;26603;26604	chr2:178714397;178714396;178714395	chr2:179579124;179579123;179579122
N2AB	8476	25651;25652;25653	chr2:178714397;178714396;178714395	chr2:179579124;179579123;179579122
N2A	7549	22870;22871;22872	chr2:178714397;178714396;178714395	chr2:179579124;179579123;179579122
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-73
• Domain position: 58
• Structural Position: 137
• Q(SASA): 0.2091
• 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
T/A	rs776154251	-1.493	0.001	D	0.28	0.241	0.255270683199	gnomAD-2.1.1	5.37E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	5.59642E-04	7.85E-06	0
T/A	rs776154251	-1.493	0.001	D	0.28	0.241	0.255270683199	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	0	0	0	0	0	None	1.88324E-04	0	1.47E-05	0	0
T/A	rs776154251	-1.493	0.001	D	0.28	0.241	0.255270683199	gnomAD-4.0.0	1.54926E-05	None	None	None	None	N	None	0	0	None	0	0	None	2.96856E-04	0	5.08581E-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
T/A	0.0765	likely_benign	0.0853	benign	-1.048	Destabilizing	0.001	N	0.28	neutral	D	0.532792972	None	None	N
T/C	0.3645	ambiguous	0.4341	ambiguous	-0.881	Destabilizing	0.952	D	0.589	neutral	None	None	None	None	N
T/D	0.4129	ambiguous	0.5242	ambiguous	-1.803	Destabilizing	0.428	N	0.609	neutral	None	None	None	None	N
T/E	0.2623	likely_benign	0.3329	benign	-1.605	Destabilizing	0.416	N	0.584	neutral	None	None	None	None	N
T/F	0.1566	likely_benign	0.2043	benign	-0.678	Destabilizing	0.903	D	0.619	neutral	None	None	None	None	N
T/G	0.2411	likely_benign	0.3109	benign	-1.46	Destabilizing	0.472	N	0.566	neutral	None	None	None	None	N
T/H	0.1894	likely_benign	0.2384	benign	-1.667	Destabilizing	0.988	D	0.607	neutral	None	None	None	None	N
T/I	0.1159	likely_benign	0.1385	benign	0.031	Stabilizing	0.115	N	0.533	neutral	N	0.492550227	None	None	N
T/K	0.1526	likely_benign	0.1951	benign	-0.642	Destabilizing	0.499	N	0.582	neutral	None	None	None	None	N
T/L	0.0789	likely_benign	0.0967	benign	0.031	Stabilizing	0.003	N	0.449	neutral	None	None	None	None	N
T/M	0.0842	likely_benign	0.0956	benign	-0.03	Destabilizing	0.777	D	0.611	neutral	None	None	None	None	N
T/N	0.1301	likely_benign	0.1641	benign	-1.371	Destabilizing	0.361	N	0.589	neutral	N	0.507096083	None	None	N
T/P	0.6117	likely_pathogenic	0.756	pathogenic	-0.297	Destabilizing	0.534	D	0.599	neutral	D	0.530569162	None	None	N
T/Q	0.1749	likely_benign	0.2149	benign	-1.127	Destabilizing	0.768	D	0.608	neutral	None	None	None	None	N
T/R	0.1189	likely_benign	0.148	benign	-0.873	Destabilizing	0.903	D	0.607	neutral	None	None	None	None	N
T/S	0.0975	likely_benign	0.1143	benign	-1.497	Destabilizing	0.001	N	0.433	neutral	N	0.482940155	None	None	N
T/V	0.1004	likely_benign	0.112	benign	-0.297	Destabilizing	0.002	N	0.43	neutral	None	None	None	None	N
T/W	0.4812	ambiguous	0.5782	pathogenic	-0.926	Destabilizing	0.995	D	0.659	neutral	None	None	None	None	N
T/Y	0.2081	likely_benign	0.2548	benign	-0.519	Destabilizing	0.95	D	0.624	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.