TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32164	96715;96716;96717	chr2:178543483;178543482;178543481	chr2:179408210;179408209;179408208
N2AB	30523	91792;91793;91794	chr2:178543483;178543482;178543481	chr2:179408210;179408209;179408208
N2A	29596	89011;89012;89013	chr2:178543483;178543482;178543481	chr2:179408210;179408209;179408208
N2B	23099	69520;69521;69522	chr2:178543483;178543482;178543481	chr2:179408210;179408209;179408208
Novex-1	23224	69895;69896;69897	chr2:178543483;178543482;178543481	chr2:179408210;179408209;179408208
Novex-2	23291	70096;70097;70098	chr2:178543483;178543482;178543481	chr2:179408210;179408209;179408208
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Fn3-122
• Domain position: 60
• Structural Position: 91
• Q(SASA): 0.2746
• 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
Y/H	rs1374040247	-1.343	0.99	N	0.545	0.491	0.390531646278	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
Y/H	rs1374040247	-1.343	0.99	N	0.545	0.491	0.390531646278	gnomAD-4.0.0	3.18287E-06	None	None	None	None	N	None	0	2.28697E-05	None	0	0	None	0	0	2.85837E-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
Y/A	0.7144	likely_pathogenic	0.6296	pathogenic	-2.35	Highly Destabilizing	0.86	D	0.571	neutral	None	None	None	None	N
Y/C	0.1281	likely_benign	0.0968	benign	-1.379	Destabilizing	0.997	D	0.724	prob.delet.	N	0.433905696	None	None	N
Y/D	0.8733	likely_pathogenic	0.8281	pathogenic	-1.958	Destabilizing	0.99	D	0.735	prob.delet.	N	0.499671392	None	None	N
Y/E	0.9153	likely_pathogenic	0.8887	pathogenic	-1.791	Destabilizing	0.993	D	0.683	prob.neutral	None	None	None	None	N
Y/F	0.0691	likely_benign	0.0698	benign	-0.684	Destabilizing	0.014	N	0.22	neutral	N	0.430459959	None	None	N
Y/G	0.7185	likely_pathogenic	0.6409	pathogenic	-2.731	Highly Destabilizing	0.978	D	0.66	neutral	None	None	None	None	N
Y/H	0.2494	likely_benign	0.2273	benign	-1.186	Destabilizing	0.99	D	0.545	neutral	N	0.491817849	None	None	N
Y/I	0.5845	likely_pathogenic	0.521	ambiguous	-1.14	Destabilizing	0.754	D	0.525	neutral	None	None	None	None	N
Y/K	0.894	likely_pathogenic	0.861	pathogenic	-1.801	Destabilizing	0.978	D	0.685	prob.neutral	None	None	None	None	N
Y/L	0.4231	ambiguous	0.3704	ambiguous	-1.14	Destabilizing	0.019	N	0.473	neutral	None	None	None	None	N
Y/M	0.6433	likely_pathogenic	0.6018	pathogenic	-0.919	Destabilizing	0.956	D	0.669	neutral	None	None	None	None	N
Y/N	0.6082	likely_pathogenic	0.5389	ambiguous	-2.482	Highly Destabilizing	0.99	D	0.703	prob.neutral	N	0.499417902	None	None	N
Y/P	0.9833	likely_pathogenic	0.9738	pathogenic	-1.547	Destabilizing	0.993	D	0.741	deleterious	None	None	None	None	N
Y/Q	0.7269	likely_pathogenic	0.6756	pathogenic	-2.235	Highly Destabilizing	0.993	D	0.658	neutral	None	None	None	None	N
Y/R	0.786	likely_pathogenic	0.7266	pathogenic	-1.569	Destabilizing	0.978	D	0.701	prob.neutral	None	None	None	None	N
Y/S	0.514	ambiguous	0.4245	ambiguous	-2.903	Highly Destabilizing	0.97	D	0.624	neutral	N	0.487808107	None	None	N
Y/T	0.7369	likely_pathogenic	0.6671	pathogenic	-2.625	Highly Destabilizing	0.978	D	0.629	neutral	None	None	None	None	N
Y/V	0.4897	ambiguous	0.4201	ambiguous	-1.547	Destabilizing	0.754	D	0.51	neutral	None	None	None	None	N
Y/W	0.3785	ambiguous	0.3779	ambiguous	-0.153	Destabilizing	0.998	D	0.554	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.