TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2365	7318;7319;7320	chr2:178774075;178774074;178774073	chr2:179638802;179638801;179638800
N2AB	2365	7318;7319;7320	chr2:178774075;178774074;178774073	chr2:179638802;179638801;179638800
N2A	2365	7318;7319;7320	chr2:178774075;178774074;178774073	chr2:179638802;179638801;179638800
N2B	2319	7180;7181;7182	chr2:178774075;178774074;178774073	chr2:179638802;179638801;179638800
Novex-1	2319	7180;7181;7182	chr2:178774075;178774074;178774073	chr2:179638802;179638801;179638800
Novex-2	2319	7180;7181;7182	chr2:178774075;178774074;178774073	chr2:179638802;179638801;179638800
Novex-3	2365	7318;7319;7320	chr2:178774075;178774074;178774073	chr2:179638802;179638801;179638800

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAA
• RefSeq wild type template codon: GTT
• Domain: Ig-13
• Domain position: 10
• Structural Position: 13
• Q(SASA): 0.4981
• 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/H	rs755961734	-0.563	0.991	D	0.347	0.31	0.339074221408	gnomAD-2.1.1	3.99E-06	None	None	None	None	N	None	0	2.89E-05	None	0	0	None	0	None	0	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	0.4422	ambiguous	0.4355	ambiguous	-0.065	Destabilizing	0.85	D	0.28	neutral	None	None	None	None	N
Q/C	0.7803	likely_pathogenic	0.7767	pathogenic	0.054	Stabilizing	0.998	D	0.369	neutral	None	None	None	None	N
Q/D	0.7587	likely_pathogenic	0.7627	pathogenic	0.153	Stabilizing	0.977	D	0.282	neutral	None	None	None	None	N
Q/E	0.1485	likely_benign	0.1448	benign	0.13	Stabilizing	0.929	D	0.243	neutral	N	0.50917363	None	None	N
Q/F	0.8483	likely_pathogenic	0.8555	pathogenic	-0.344	Destabilizing	0.021	N	0.279	neutral	None	None	None	None	N
Q/G	0.6128	likely_pathogenic	0.6084	pathogenic	-0.232	Destabilizing	0.977	D	0.347	neutral	None	None	None	None	N
Q/H	0.3787	ambiguous	0.3825	ambiguous	-0.093	Destabilizing	0.991	D	0.347	neutral	D	0.540958484	None	None	N
Q/I	0.4716	ambiguous	0.4797	ambiguous	0.281	Stabilizing	0.584	D	0.297	neutral	None	None	None	None	N
Q/K	0.1415	likely_benign	0.1366	benign	0.128	Stabilizing	0.969	D	0.237	neutral	N	0.509024163	None	None	N
Q/L	0.2434	likely_benign	0.2445	benign	0.281	Stabilizing	0.002	N	0.186	neutral	N	0.430964215	None	None	N
Q/M	0.4414	ambiguous	0.4348	ambiguous	0.267	Stabilizing	0.96	D	0.327	neutral	None	None	None	None	N
Q/N	0.5578	ambiguous	0.5692	pathogenic	-0.221	Destabilizing	0.977	D	0.319	neutral	None	None	None	None	N
Q/P	0.8759	likely_pathogenic	0.8885	pathogenic	0.193	Stabilizing	0.991	D	0.425	neutral	D	0.582767675	None	None	N
Q/R	0.1669	likely_benign	0.1629	benign	0.233	Stabilizing	0.969	D	0.265	neutral	N	0.500449263	None	None	N
Q/S	0.5051	ambiguous	0.5116	ambiguous	-0.194	Destabilizing	0.977	D	0.202	neutral	None	None	None	None	N
Q/T	0.315	likely_benign	0.3175	benign	-0.065	Destabilizing	0.932	D	0.301	neutral	None	None	None	None	N
Q/V	0.321	likely_benign	0.3197	benign	0.193	Stabilizing	0.584	D	0.263	neutral	None	None	None	None	N
Q/W	0.8151	likely_pathogenic	0.8186	pathogenic	-0.388	Destabilizing	0.998	D	0.359	neutral	None	None	None	None	N
Q/Y	0.7033	likely_pathogenic	0.7162	pathogenic	-0.092	Destabilizing	0.773	D	0.387	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.