TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18100	54523;54524;54525	chr2:178604791;178604790;178604789	chr2:179469518;179469517;179469516
N2AB	16459	49600;49601;49602	chr2:178604791;178604790;178604789	chr2:179469518;179469517;179469516
N2A	15532	46819;46820;46821	chr2:178604791;178604790;178604789	chr2:179469518;179469517;179469516
N2B	9035	27328;27329;27330	chr2:178604791;178604790;178604789	chr2:179469518;179469517;179469516
Novex-1	9160	27703;27704;27705	chr2:178604791;178604790;178604789	chr2:179469518;179469517;179469516
Novex-2	9227	27904;27905;27906	chr2:178604791;178604790;178604789	chr2:179469518;179469517;179469516
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-19
• Domain position: 36
• Structural Position: 38
• Q(SASA): 0.1437
• 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/S	None	None	1.0	D	0.883	0.907	0.915559038057	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05

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	0.9957	likely_pathogenic	0.9968	pathogenic	-3.481	Highly Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	N
Y/C	0.8993	likely_pathogenic	0.9213	pathogenic	-1.862	Destabilizing	1.0	D	0.855	deleterious	D	0.614723338	None	None	N
Y/D	0.9964	likely_pathogenic	0.9971	pathogenic	-3.896	Highly Destabilizing	1.0	D	0.872	deleterious	D	0.631378472	None	None	N
Y/E	0.999	likely_pathogenic	0.9993	pathogenic	-3.684	Highly Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	N
Y/F	0.213	likely_benign	0.249	benign	-1.559	Destabilizing	0.999	D	0.679	prob.neutral	D	0.537151779	None	None	N
Y/G	0.9902	likely_pathogenic	0.9929	pathogenic	-3.868	Highly Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
Y/H	0.9577	likely_pathogenic	0.9728	pathogenic	-2.714	Highly Destabilizing	1.0	D	0.797	deleterious	D	0.614723338	None	None	N
Y/I	0.9673	likely_pathogenic	0.9752	pathogenic	-2.156	Highly Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
Y/K	0.9987	likely_pathogenic	0.9991	pathogenic	-2.583	Highly Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	N
Y/L	0.9427	likely_pathogenic	0.9495	pathogenic	-2.156	Highly Destabilizing	0.999	D	0.747	deleterious	None	None	None	None	N
Y/M	0.9822	likely_pathogenic	0.9866	pathogenic	-1.808	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
Y/N	0.98	likely_pathogenic	0.9855	pathogenic	-3.398	Highly Destabilizing	1.0	D	0.867	deleterious	D	0.631378472	None	None	N
Y/P	0.9994	likely_pathogenic	0.9993	pathogenic	-2.618	Highly Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
Y/Q	0.9976	likely_pathogenic	0.9984	pathogenic	-3.123	Highly Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
Y/R	0.9935	likely_pathogenic	0.9953	pathogenic	-2.392	Highly Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	N
Y/S	0.9847	likely_pathogenic	0.9885	pathogenic	-3.643	Highly Destabilizing	1.0	D	0.883	deleterious	D	0.631378472	None	None	N
Y/T	0.9927	likely_pathogenic	0.9951	pathogenic	-3.317	Highly Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	N
Y/V	0.9472	likely_pathogenic	0.9567	pathogenic	-2.618	Highly Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
Y/W	0.7975	likely_pathogenic	0.7953	pathogenic	-0.858	Destabilizing	1.0	D	0.793	deleterious	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.