TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30551	91876;91877;91878	chr2:178550187;178550186;178550185	chr2:179414914;179414913;179414912
N2AB	28910	86953;86954;86955	chr2:178550187;178550186;178550185	chr2:179414914;179414913;179414912
N2A	27983	84172;84173;84174	chr2:178550187;178550186;178550185	chr2:179414914;179414913;179414912
N2B	21486	64681;64682;64683	chr2:178550187;178550186;178550185	chr2:179414914;179414913;179414912
Novex-1	21611	65056;65057;65058	chr2:178550187;178550186;178550185	chr2:179414914;179414913;179414912
Novex-2	21678	65257;65258;65259	chr2:178550187;178550186;178550185	chr2:179414914;179414913;179414912
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAA
• RefSeq wild type template codon: GTT
• Domain: Ig-149
• Domain position: 20
• Structural Position: 38
• Q(SASA): 0.9975
• Predicted PPI site: I

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
Q/K	None	None	None	N	0.113	0.096	0.149567049428	gnomAD-4.0.0	1.20033E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
Q/R	rs775297990	0.326	None	N	0.142	0.14	0.0986583533028	gnomAD-2.1.1	8.04E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.89E-06	1.65728E-04
Q/R	rs775297990	0.326	None	N	0.142	0.14	0.0986583533028	gnomAD-4.0.0	2.73687E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79899E-06	0	3.3129E-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
Q/A	0.211	likely_benign	0.2236	benign	-0.067	Destabilizing	0.002	N	0.187	neutral	None	None	None	None	I
Q/C	0.6385	likely_pathogenic	0.6316	pathogenic	-0.374	Destabilizing	0.497	N	0.257	neutral	None	None	None	None	I
Q/D	0.4437	ambiguous	0.462	ambiguous	-0.193	Destabilizing	0.018	N	0.185	neutral	None	None	None	None	I
Q/E	0.1054	likely_benign	0.1051	benign	-0.244	Destabilizing	0.003	N	0.156	neutral	N	0.42104076	None	None	I
Q/F	0.6671	likely_pathogenic	0.6794	pathogenic	-0.537	Destabilizing	0.245	N	0.345	neutral	None	None	None	None	I
Q/G	0.2946	likely_benign	0.3047	benign	-0.143	Destabilizing	0.008	N	0.237	neutral	None	None	None	None	I
Q/H	0.1984	likely_benign	0.2037	benign	0.127	Stabilizing	0.196	N	0.252	neutral	N	0.500485766	None	None	I
Q/I	0.4138	ambiguous	0.4194	ambiguous	0.036	Stabilizing	0.044	N	0.395	neutral	None	None	None	None	I
Q/K	0.0996	likely_benign	0.0951	benign	-0.101	Destabilizing	None	N	0.113	neutral	N	0.440666671	None	None	I
Q/L	0.1514	likely_benign	0.1552	benign	0.036	Stabilizing	0.007	N	0.218	neutral	N	0.454252044	None	None	I
Q/M	0.3566	ambiguous	0.3666	ambiguous	-0.147	Destabilizing	0.497	N	0.264	neutral	None	None	None	None	I
Q/N	0.2726	likely_benign	0.301	benign	-0.462	Destabilizing	0.018	N	0.185	neutral	None	None	None	None	I
Q/P	0.695	likely_pathogenic	0.6686	pathogenic	0.023	Stabilizing	0.065	N	0.307	neutral	D	0.525440138	None	None	I
Q/R	0.1091	likely_benign	0.1057	benign	0.107	Stabilizing	None	N	0.142	neutral	N	0.440456027	None	None	I
Q/S	0.2079	likely_benign	0.2206	benign	-0.413	Destabilizing	None	N	0.111	neutral	None	None	None	None	I
Q/T	0.1569	likely_benign	0.1678	benign	-0.351	Destabilizing	None	N	0.109	neutral	None	None	None	None	I
Q/V	0.2631	likely_benign	0.2735	benign	0.023	Stabilizing	0.009	N	0.217	neutral	None	None	None	None	I
Q/W	0.6241	likely_pathogenic	0.6195	pathogenic	-0.652	Destabilizing	0.788	D	0.265	neutral	None	None	None	None	I
Q/Y	0.459	ambiguous	0.4695	ambiguous	-0.343	Destabilizing	0.497	N	0.337	neutral	None	None	None	None	I

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.