TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	10079	30460;30461;30462	chr2:178702652;178702651;178702650	chr2:179567379;179567378;179567377
N2AB	9762	29509;29510;29511	chr2:178702652;178702651;178702650	chr2:179567379;179567378;179567377
N2A	8835	26728;26729;26730	chr2:178702652;178702651;178702650	chr2:179567379;179567378;179567377
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: Q
• RefSeq wild type transcript codon: CAG
• RefSeq wild type template codon: GTC
• Domain: Ig-86
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.2442
• 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	rs752672136	0.344	0.92	None	0.293	0.287	0.238096912614	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
Q/R	rs752672136	0.344	0.92	None	0.293	0.287	0.238096912614	gnomAD-4.0.0	1.59282E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86257E-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
Q/A	0.4915	ambiguous	0.5158	ambiguous	-0.339	Destabilizing	0.863	D	0.227	neutral	None	None	None	None	N
Q/C	0.9082	likely_pathogenic	0.9141	pathogenic	0.009	Stabilizing	0.999	D	0.385	neutral	None	None	None	None	N
Q/D	0.8453	likely_pathogenic	0.8717	pathogenic	0.321	Stabilizing	0.759	D	0.249	neutral	None	None	None	None	N
Q/E	0.1872	likely_benign	0.1957	benign	0.345	Stabilizing	0.061	N	0.101	neutral	None	None	None	None	N
Q/F	0.8978	likely_pathogenic	0.8979	pathogenic	-0.4	Destabilizing	0.991	D	0.381	neutral	None	None	None	None	N
Q/G	0.7371	likely_pathogenic	0.7896	pathogenic	-0.573	Destabilizing	0.969	D	0.257	neutral	None	None	None	None	N
Q/H	0.4682	ambiguous	0.485	ambiguous	-0.279	Destabilizing	0.015	N	0.107	neutral	None	None	None	None	N
Q/I	0.6577	likely_pathogenic	0.6473	pathogenic	0.202	Stabilizing	0.997	D	0.383	neutral	None	None	None	None	N
Q/K	0.2668	likely_benign	0.2525	benign	0.146	Stabilizing	0.826	D	0.268	neutral	None	None	None	None	N
Q/L	0.353	ambiguous	0.367	ambiguous	0.202	Stabilizing	0.959	D	0.249	neutral	None	None	None	None	N
Q/M	0.657	likely_pathogenic	0.6501	pathogenic	0.309	Stabilizing	0.997	D	0.337	neutral	None	None	None	None	N
Q/N	0.6295	likely_pathogenic	0.6625	pathogenic	-0.385	Destabilizing	0.939	D	0.257	neutral	None	None	None	None	N
Q/P	0.9338	likely_pathogenic	0.9579	pathogenic	0.051	Stabilizing	0.996	D	0.337	neutral	None	None	None	None	N
Q/R	0.2241	likely_benign	0.2245	benign	0.263	Stabilizing	0.92	D	0.293	neutral	None	None	None	None	N
Q/S	0.4993	ambiguous	0.546	ambiguous	-0.439	Destabilizing	0.863	D	0.256	neutral	None	None	None	None	N
Q/T	0.4002	ambiguous	0.4052	ambiguous	-0.231	Destabilizing	0.969	D	0.257	neutral	None	None	None	None	N
Q/V	0.4927	ambiguous	0.4836	ambiguous	0.051	Stabilizing	0.969	D	0.293	neutral	None	None	None	None	N
Q/W	0.8964	likely_pathogenic	0.9073	pathogenic	-0.324	Destabilizing	0.999	D	0.365	neutral	None	None	None	None	N
Q/Y	0.81	likely_pathogenic	0.8068	pathogenic	-0.07	Destabilizing	0.939	D	0.344	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.