TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22648	68167;68168;68169	chr2:178579088;178579087;178579086	chr2:179443815;179443814;179443813
N2AB	21007	63244;63245;63246	chr2:178579088;178579087;178579086	chr2:179443815;179443814;179443813
N2A	20080	60463;60464;60465	chr2:178579088;178579087;178579086	chr2:179443815;179443814;179443813
N2B	13583	40972;40973;40974	chr2:178579088;178579087;178579086	chr2:179443815;179443814;179443813
Novex-1	13708	41347;41348;41349	chr2:178579088;178579087;178579086	chr2:179443815;179443814;179443813
Novex-2	13775	41548;41549;41550	chr2:178579088;178579087;178579086	chr2:179443815;179443814;179443813
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: Fn3-52
• Domain position: 6
• Structural Position: 6
• Q(SASA): 0.2464
• 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
T/N	None	None	0.998	N	0.692	0.233	0.283761946502	gnomAD-4.0.0	1.71096E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.24906E-05	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	0.0769	likely_benign	0.0744	benign	-0.627	Destabilizing	0.962	D	0.505	neutral	N	0.465193316	None	None	N
T/C	0.325	likely_benign	0.3151	benign	-0.393	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
T/D	0.3973	ambiguous	0.3623	ambiguous	-0.159	Destabilizing	0.998	D	0.693	prob.neutral	None	None	None	None	N
T/E	0.2511	likely_benign	0.2294	benign	-0.134	Destabilizing	0.998	D	0.689	prob.neutral	None	None	None	None	N
T/F	0.3094	likely_benign	0.2873	benign	-0.592	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
T/G	0.1994	likely_benign	0.1994	benign	-0.913	Destabilizing	0.994	D	0.619	neutral	None	None	None	None	N
T/H	0.3227	likely_benign	0.2997	benign	-1.234	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
T/I	0.154	likely_benign	0.1368	benign	0.047	Stabilizing	0.999	D	0.782	deleterious	N	0.472388648	None	None	N
T/K	0.2118	likely_benign	0.1895	benign	-0.761	Destabilizing	0.998	D	0.698	prob.neutral	None	None	None	None	N
T/L	0.1043	likely_benign	0.1013	benign	0.047	Stabilizing	0.997	D	0.596	neutral	None	None	None	None	N
T/M	0.0959	likely_benign	0.0924	benign	0.128	Stabilizing	1.0	D	0.756	deleterious	None	None	None	None	N
T/N	0.1564	likely_benign	0.1462	benign	-0.717	Destabilizing	0.998	D	0.692	prob.neutral	N	0.432390252	None	None	N
T/P	0.3422	ambiguous	0.3648	ambiguous	-0.144	Destabilizing	0.999	D	0.779	deleterious	N	0.383654942	None	None	N
T/Q	0.2164	likely_benign	0.2031	benign	-0.756	Destabilizing	0.999	D	0.782	deleterious	None	None	None	None	N
T/R	0.1901	likely_benign	0.1695	benign	-0.656	Destabilizing	0.999	D	0.773	deleterious	None	None	None	None	N
T/S	0.1044	likely_benign	0.1006	benign	-0.94	Destabilizing	0.825	D	0.329	neutral	N	0.422173258	None	None	N
T/V	0.1011	likely_benign	0.097	benign	-0.144	Destabilizing	0.997	D	0.576	neutral	None	None	None	None	N
T/W	0.6756	likely_pathogenic	0.6627	pathogenic	-0.625	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
T/Y	0.3674	ambiguous	0.346	ambiguous	-0.373	Destabilizing	1.0	D	0.817	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.