TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21555	64888;64889;64890	chr2:178585081;178585080;178585079	chr2:179449808;179449807;179449806
N2AB	19914	59965;59966;59967	chr2:178585081;178585080;178585079	chr2:179449808;179449807;179449806
N2A	18987	57184;57185;57186	chr2:178585081;178585080;178585079	chr2:179449808;179449807;179449806
N2B	12490	37693;37694;37695	chr2:178585081;178585080;178585079	chr2:179449808;179449807;179449806
Novex-1	12615	38068;38069;38070	chr2:178585081;178585080;178585079	chr2:179449808;179449807;179449806
Novex-2	12682	38269;38270;38271	chr2:178585081;178585080;178585079	chr2:179449808;179449807;179449806
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Ig-124
• Domain position: 87
• Structural Position: 175
• Q(SASA): 0.4119
• 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
V/A	rs756320940	-0.905	0.027	N	0.311	0.098	0.343560092441	gnomAD-2.1.1	4.11E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.03E-06	0
V/A	rs756320940	-0.905	0.027	N	0.311	0.098	0.343560092441	gnomAD-4.0.0	1.37635E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.80548E-06	0	0
V/L	None	None	0.004	N	0.245	0.125	0.275215494804	gnomAD-4.0.0	1.61303E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.89198E-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
V/A	0.1732	likely_benign	0.1787	benign	-1.349	Destabilizing	0.027	N	0.311	neutral	N	0.50712095	None	None	N
V/C	0.6302	likely_pathogenic	0.6329	pathogenic	-0.911	Destabilizing	0.824	D	0.431	neutral	None	None	None	None	N
V/D	0.4467	ambiguous	0.4397	ambiguous	-1.046	Destabilizing	0.38	N	0.548	neutral	None	None	None	None	N
V/E	0.3897	ambiguous	0.3818	ambiguous	-1.075	Destabilizing	0.117	N	0.509	neutral	N	0.452190387	None	None	N
V/F	0.162	likely_benign	0.1535	benign	-1.079	Destabilizing	0.38	N	0.465	neutral	None	None	None	None	N
V/G	0.3482	ambiguous	0.3552	ambiguous	-1.638	Destabilizing	0.117	N	0.567	neutral	D	0.522245118	None	None	N
V/H	0.4367	ambiguous	0.4427	ambiguous	-1.115	Destabilizing	0.935	D	0.524	neutral	None	None	None	None	N
V/I	0.0581	likely_benign	0.0577	benign	-0.669	Destabilizing	None	N	0.09	neutral	N	0.419811396	None	None	N
V/K	0.4106	ambiguous	0.4045	ambiguous	-1.096	Destabilizing	0.149	N	0.507	neutral	None	None	None	None	N
V/L	0.1337	likely_benign	0.1336	benign	-0.669	Destabilizing	0.004	N	0.245	neutral	N	0.482572009	None	None	N
V/M	0.0984	likely_benign	0.1007	benign	-0.494	Destabilizing	0.38	N	0.411	neutral	None	None	None	None	N
V/N	0.1905	likely_benign	0.1962	benign	-0.829	Destabilizing	0.38	N	0.546	neutral	None	None	None	None	N
V/P	0.9282	likely_pathogenic	0.9468	pathogenic	-0.86	Destabilizing	0.555	D	0.519	neutral	None	None	None	None	N
V/Q	0.3144	likely_benign	0.3176	benign	-1.041	Destabilizing	0.555	D	0.532	neutral	None	None	None	None	N
V/R	0.3568	ambiguous	0.358	ambiguous	-0.54	Destabilizing	0.38	N	0.567	neutral	None	None	None	None	N
V/S	0.1781	likely_benign	0.1851	benign	-1.357	Destabilizing	0.081	N	0.501	neutral	None	None	None	None	N
V/T	0.0986	likely_benign	0.0976	benign	-1.28	Destabilizing	None	N	0.076	neutral	None	None	None	None	N
V/W	0.7393	likely_pathogenic	0.7499	pathogenic	-1.211	Destabilizing	0.935	D	0.576	neutral	None	None	None	None	N
V/Y	0.4602	ambiguous	0.4573	ambiguous	-0.939	Destabilizing	0.555	D	0.466	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.