TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35462	106609;106610;106611	chr2:178530107;178530106;178530105	chr2:179394834;179394833;179394832
N2AB	33821	101686;101687;101688	chr2:178530107;178530106;178530105	chr2:179394834;179394833;179394832
N2A	32894	98905;98906;98907	chr2:178530107;178530106;178530105	chr2:179394834;179394833;179394832
N2B	26397	79414;79415;79416	chr2:178530107;178530106;178530105	chr2:179394834;179394833;179394832
Novex-1	26522	79789;79790;79791	chr2:178530107;178530106;178530105	chr2:179394834;179394833;179394832
Novex-2	26589	79990;79991;79992	chr2:178530107;178530106;178530105	chr2:179394834;179394833;179394832
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-166
• Domain position: 43
• Structural Position: 70
• Q(SASA): 0.2257
• 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
Q/R	rs376392819	None	0.001	N	0.145	0.201	None	gnomAD-3.1.2	3.94E-05	None	None	None	None	N	None	1.44746E-04	0	0	0	0	None	0	0	0	0	0
Q/R	rs376392819	None	0.001	N	0.145	0.201	None	gnomAD-4.0.0	5.6268E-06	None	None	None	None	N	None	1.08213E-04	0	None	0	0	None	0	0	8.50044E-07	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
Q/A	0.1186	likely_benign	0.1178	benign	-0.155	Destabilizing	0.206	N	0.457	neutral	None	None	None	None	N
Q/C	0.6355	likely_pathogenic	0.6231	pathogenic	0.102	Stabilizing	0.981	D	0.513	neutral	None	None	None	None	N
Q/D	0.2404	likely_benign	0.2371	benign	0.264	Stabilizing	0.386	N	0.399	neutral	None	None	None	None	N
Q/E	0.0651	likely_benign	0.0671	benign	0.24	Stabilizing	0.164	N	0.407	neutral	N	0.437183649	None	None	N
Q/F	0.6152	likely_pathogenic	0.6018	pathogenic	-0.4	Destabilizing	0.932	D	0.502	neutral	None	None	None	None	N
Q/G	0.183	likely_benign	0.1776	benign	-0.326	Destabilizing	0.386	N	0.464	neutral	None	None	None	None	N
Q/H	0.1875	likely_benign	0.1871	benign	-0.166	Destabilizing	0.771	D	0.433	neutral	N	0.480091851	None	None	N
Q/I	0.2981	likely_benign	0.2985	benign	0.202	Stabilizing	0.817	D	0.501	neutral	None	None	None	None	N
Q/K	0.0827	likely_benign	0.0838	benign	0.189	Stabilizing	0.089	N	0.455	neutral	N	0.474125884	None	None	N
Q/L	0.1318	likely_benign	0.1314	benign	0.202	Stabilizing	0.322	N	0.464	neutral	N	0.450462377	None	None	N
Q/M	0.3233	likely_benign	0.3291	benign	0.322	Stabilizing	0.932	D	0.431	neutral	None	None	None	None	N
Q/N	0.211	likely_benign	0.2083	benign	-0.226	Destabilizing	0.386	N	0.425	neutral	None	None	None	None	N
Q/P	0.0832	likely_benign	0.0808	benign	0.11	Stabilizing	0.771	D	0.423	neutral	N	0.412616065	None	None	N
Q/R	0.0996	likely_benign	0.0993	benign	0.301	Stabilizing	0.001	N	0.145	neutral	N	0.472125729	None	None	N
Q/S	0.1448	likely_benign	0.1451	benign	-0.221	Destabilizing	0.386	N	0.419	neutral	None	None	None	None	N
Q/T	0.1403	likely_benign	0.1396	benign	-0.087	Destabilizing	0.386	N	0.425	neutral	None	None	None	None	N
Q/V	0.2038	likely_benign	0.2092	benign	0.11	Stabilizing	0.386	N	0.445	neutral	None	None	None	None	N
Q/W	0.4469	ambiguous	0.4486	ambiguous	-0.399	Destabilizing	0.981	D	0.518	neutral	None	None	None	None	N
Q/Y	0.4022	ambiguous	0.3973	ambiguous	-0.12	Destabilizing	0.932	D	0.459	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.