TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32149	96670;96671;96672	chr2:178543528;178543527;178543526	chr2:179408255;179408254;179408253
N2AB	30508	91747;91748;91749	chr2:178543528;178543527;178543526	chr2:179408255;179408254;179408253
N2A	29581	88966;88967;88968	chr2:178543528;178543527;178543526	chr2:179408255;179408254;179408253
N2B	23084	69475;69476;69477	chr2:178543528;178543527;178543526	chr2:179408255;179408254;179408253
Novex-1	23209	69850;69851;69852	chr2:178543528;178543527;178543526	chr2:179408255;179408254;179408253
Novex-2	23276	70051;70052;70053	chr2:178543528;178543527;178543526	chr2:179408255;179408254;179408253
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: M
• RefSeq wild type transcript codon: ATG
• RefSeq wild type template codon: TAC
• Domain: Fn3-122
• Domain position: 45
• Structural Position: 60
• Q(SASA): 0.5936
• 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
M/I	rs886042242	0.213	0.828	N	0.369	0.254	0.530948259028	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
M/I	rs886042242	0.213	0.828	N	0.369	0.254	0.530948259028	gnomAD-4.0.0	1.59257E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43308E-05	0
M/R	rs766743444	None	0.998	N	0.329	0.527	0.625177984591	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
M/R	rs766743444	None	0.998	N	0.329	0.527	0.625177984591	gnomAD-4.0.0	4.96064E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	6.7841E-06	0	0
M/T	rs766743444	0.465	0.979	N	0.292	0.457	0.637230306968	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
M/T	rs766743444	0.465	0.979	N	0.292	0.457	0.637230306968	gnomAD-4.0.0	2.0538E-06	None	None	None	None	I	None	0	0	None	0	5.04465E-05	None	0	0	8.99776E-07	0	0
M/V	rs972033083	0.066	0.828	N	0.307	0.242	0.517322629239	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
M/V	rs972033083	0.066	0.828	N	0.307	0.242	0.517322629239	gnomAD-4.0.0	4.77794E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.71765E-06	1.43312E-05	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
M/A	0.5656	likely_pathogenic	0.5013	ambiguous	-0.536	Destabilizing	0.963	D	0.326	neutral	None	None	None	None	I
M/C	0.7359	likely_pathogenic	0.7648	pathogenic	-0.407	Destabilizing	1.0	D	0.331	neutral	None	None	None	None	I
M/D	0.952	likely_pathogenic	0.9491	pathogenic	0.286	Stabilizing	0.999	D	0.421	neutral	None	None	None	None	I
M/E	0.7843	likely_pathogenic	0.7652	pathogenic	0.231	Stabilizing	0.999	D	0.365	neutral	None	None	None	None	I
M/F	0.5212	ambiguous	0.4815	ambiguous	-0.173	Destabilizing	0.969	D	0.295	neutral	None	None	None	None	I
M/G	0.6482	likely_pathogenic	0.6381	pathogenic	-0.717	Destabilizing	0.999	D	0.404	neutral	None	None	None	None	I
M/H	0.6398	likely_pathogenic	0.6385	pathogenic	0.108	Stabilizing	1.0	D	0.401	neutral	None	None	None	None	I
M/I	0.8051	likely_pathogenic	0.7351	pathogenic	-0.151	Destabilizing	0.828	D	0.369	neutral	N	0.478133689	None	None	I
M/K	0.3276	likely_benign	0.31	benign	0.378	Stabilizing	0.993	D	0.34	neutral	N	0.396688528	None	None	I
M/L	0.1753	likely_benign	0.1549	benign	-0.151	Destabilizing	0.03	N	0.128	neutral	N	0.477440256	None	None	I
M/N	0.6816	likely_pathogenic	0.6621	pathogenic	0.572	Stabilizing	0.999	D	0.391	neutral	None	None	None	None	I
M/P	0.9643	likely_pathogenic	0.9546	pathogenic	-0.25	Destabilizing	0.999	D	0.387	neutral	None	None	None	None	I
M/Q	0.3011	likely_benign	0.2988	benign	0.385	Stabilizing	0.999	D	0.287	neutral	None	None	None	None	I
M/R	0.3431	ambiguous	0.3195	benign	0.883	Stabilizing	0.998	D	0.329	neutral	N	0.355343338	None	None	I
M/S	0.5421	ambiguous	0.4944	ambiguous	0.094	Stabilizing	0.995	D	0.335	neutral	None	None	None	None	I
M/T	0.471	ambiguous	0.4053	ambiguous	0.14	Stabilizing	0.979	D	0.292	neutral	N	0.382585868	None	None	I
M/V	0.1985	likely_benign	0.1584	benign	-0.25	Destabilizing	0.828	D	0.307	neutral	N	0.437113786	None	None	I
M/W	0.804	likely_pathogenic	0.7836	pathogenic	-0.127	Destabilizing	1.0	D	0.38	neutral	None	None	None	None	I
M/Y	0.7246	likely_pathogenic	0.7051	pathogenic	0.01	Stabilizing	0.999	D	0.327	neutral	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.