TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32235	96928;96929;96930	chr2:178543270;178543269;178543268	chr2:179407997;179407996;179407995
N2AB	30594	92005;92006;92007	chr2:178543270;178543269;178543268	chr2:179407997;179407996;179407995
N2A	29667	89224;89225;89226	chr2:178543270;178543269;178543268	chr2:179407997;179407996;179407995
N2B	23170	69733;69734;69735	chr2:178543270;178543269;178543268	chr2:179407997;179407996;179407995
Novex-1	23295	70108;70109;70110	chr2:178543270;178543269;178543268	chr2:179407997;179407996;179407995
Novex-2	23362	70309;70310;70311	chr2:178543270;178543269;178543268	chr2:179407997;179407996;179407995
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-123
• Domain position: 34
• Structural Position: 36
• Q(SASA): 0.2759
• Predicted PPI site: I

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
T/I	rs1428828704	-0.325	0.999	N	0.806	0.434	0.421920138742	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	5.57E-05	None	0	None	0	0	0
T/I	rs1428828704	-0.325	0.999	N	0.806	0.434	0.421920138742	gnomAD-4.0.0	1.59113E-06	None	None	None	None	I	None	0	0	None	0	2.77254E-05	None	0	0	0	0	0
T/S	None	None	0.825	N	0.308	0.237	0.275641507738	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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
T/A	0.1104	likely_benign	0.105	benign	-0.672	Destabilizing	0.962	D	0.489	neutral	N	0.493920492	None	None	I
T/C	0.4036	ambiguous	0.3901	ambiguous	-0.42	Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	I
T/D	0.5091	ambiguous	0.4976	ambiguous	-0.47	Destabilizing	0.998	D	0.675	neutral	None	None	None	None	I
T/E	0.3909	ambiguous	0.3661	ambiguous	-0.509	Destabilizing	0.998	D	0.671	neutral	None	None	None	None	I
T/F	0.2977	likely_benign	0.2699	benign	-0.924	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	I
T/G	0.2545	likely_benign	0.2591	benign	-0.878	Destabilizing	0.994	D	0.624	neutral	None	None	None	None	I
T/H	0.2685	likely_benign	0.2652	benign	-1.244	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	I
T/I	0.1737	likely_benign	0.1445	benign	-0.226	Destabilizing	0.999	D	0.806	deleterious	N	0.473196118	None	None	I
T/K	0.2043	likely_benign	0.1967	benign	-0.708	Destabilizing	0.998	D	0.676	prob.neutral	None	None	None	None	I
T/L	0.094	likely_benign	0.0836	benign	-0.226	Destabilizing	0.997	D	0.591	neutral	None	None	None	None	I
T/M	0.0961	likely_benign	0.0854	benign	0.171	Stabilizing	1.0	D	0.788	deleterious	None	None	None	None	I
T/N	0.1509	likely_benign	0.1396	benign	-0.589	Destabilizing	0.998	D	0.686	prob.neutral	N	0.499694164	None	None	I
T/P	0.3849	ambiguous	0.3916	ambiguous	-0.344	Destabilizing	0.999	D	0.807	deleterious	D	0.535195112	None	None	I
T/Q	0.2266	likely_benign	0.2179	benign	-0.873	Destabilizing	0.999	D	0.822	deleterious	None	None	None	None	I
T/R	0.1676	likely_benign	0.1654	benign	-0.377	Destabilizing	0.999	D	0.803	deleterious	None	None	None	None	I
T/S	0.1248	likely_benign	0.1209	benign	-0.793	Destabilizing	0.825	D	0.308	neutral	N	0.473814774	None	None	I
T/V	0.1456	likely_benign	0.1304	benign	-0.344	Destabilizing	0.997	D	0.549	neutral	None	None	None	None	I
T/W	0.5644	likely_pathogenic	0.5708	pathogenic	-0.86	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	I
T/Y	0.3307	likely_benign	0.3208	benign	-0.62	Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	I

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.