TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8930	27013;27014;27015	chr2:178713346;178713345;178713344	chr2:179578073;179578072;179578071
N2AB	8613	26062;26063;26064	chr2:178713346;178713345;178713344	chr2:179578073;179578072;179578071
N2A	7686	23281;23282;23283	chr2:178713346;178713345;178713344	chr2:179578073;179578072;179578071
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: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Ig-75
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.5063
• 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
R/G	None	None	0.896	N	0.497	0.382	0.556540827966	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
R/T	rs1206653316	0.102	0.896	N	0.535	0.284	0.415313616471	gnomAD-2.1.1	3.2E-05	None	None	None	None	N	None	1.1489E-04	0	None	0	0	None	0	None	0	0	0
R/T	rs1206653316	0.102	0.896	N	0.535	0.284	0.415313616471	gnomAD-3.1.2	6.61E-06	None	None	None	None	N	None	2.42E-05	0	0	0	0	None	0	0	0	0	0
R/T	rs1206653316	0.102	0.896	N	0.535	0.284	0.415313616471	gnomAD-4.0.0	3.04786E-06	None	None	None	None	N	None	3.50238E-05	0	None	0	0	None	0	0	1.20516E-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
R/A	0.682	likely_pathogenic	0.7501	pathogenic	-0.142	Destabilizing	0.919	D	0.532	neutral	None	None	None	None	N
R/C	0.3372	likely_benign	0.4154	ambiguous	-0.103	Destabilizing	0.999	D	0.645	neutral	None	None	None	None	N
R/D	0.881	likely_pathogenic	0.9213	pathogenic	-0.014	Destabilizing	0.976	D	0.54	neutral	None	None	None	None	N
R/E	0.5429	ambiguous	0.6399	pathogenic	0.073	Stabilizing	0.851	D	0.513	neutral	None	None	None	None	N
R/F	0.7883	likely_pathogenic	0.8342	pathogenic	-0.18	Destabilizing	0.996	D	0.623	neutral	None	None	None	None	N
R/G	0.4532	ambiguous	0.5201	ambiguous	-0.395	Destabilizing	0.896	D	0.497	neutral	N	0.484326885	None	None	N
R/H	0.1866	likely_benign	0.2275	benign	-0.871	Destabilizing	0.996	D	0.547	neutral	None	None	None	None	N
R/I	0.5265	ambiguous	0.6119	pathogenic	0.506	Stabilizing	0.984	D	0.631	neutral	N	0.488479261	None	None	N
R/K	0.1235	likely_benign	0.1523	benign	-0.18	Destabilizing	0.011	N	0.173	neutral	N	0.43104711	None	None	N
R/L	0.4906	ambiguous	0.5715	pathogenic	0.506	Stabilizing	0.919	D	0.497	neutral	None	None	None	None	N
R/M	0.498	ambiguous	0.5758	pathogenic	0.112	Stabilizing	0.999	D	0.601	neutral	None	None	None	None	N
R/N	0.8392	likely_pathogenic	0.889	pathogenic	0.238	Stabilizing	0.976	D	0.518	neutral	None	None	None	None	N
R/P	0.9564	likely_pathogenic	0.9628	pathogenic	0.312	Stabilizing	0.988	D	0.613	neutral	None	None	None	None	N
R/Q	0.1488	likely_benign	0.176	benign	0.095	Stabilizing	0.976	D	0.548	neutral	None	None	None	None	N
R/S	0.7464	likely_pathogenic	0.8142	pathogenic	-0.237	Destabilizing	0.896	D	0.554	neutral	N	0.476088754	None	None	N
R/T	0.5401	ambiguous	0.6283	pathogenic	0.002	Stabilizing	0.896	D	0.535	neutral	N	0.4429949	None	None	N
R/V	0.5874	likely_pathogenic	0.6598	pathogenic	0.312	Stabilizing	0.988	D	0.621	neutral	None	None	None	None	N
R/W	0.2534	likely_benign	0.2891	benign	-0.086	Destabilizing	0.999	D	0.67	neutral	None	None	None	None	N
R/Y	0.6115	likely_pathogenic	0.6754	pathogenic	0.28	Stabilizing	0.996	D	0.615	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.