TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16242	48949;48950;48951	chr2:178614883;178614882;178614881	chr2:179479610;179479609;179479608
N2AB	14601	44026;44027;44028	chr2:178614883;178614882;178614881	chr2:179479610;179479609;179479608
N2A	13674	41245;41246;41247	chr2:178614883;178614882;178614881	chr2:179479610;179479609;179479608
N2B	7177	21754;21755;21756	chr2:178614883;178614882;178614881	chr2:179479610;179479609;179479608
Novex-1	7302	22129;22130;22131	chr2:178614883;178614882;178614881	chr2:179479610;179479609;179479608
Novex-2	7369	22330;22331;22332	chr2:178614883;178614882;178614881	chr2:179479610;179479609;179479608
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Fn3-5
• Domain position: 88
• Structural Position: 122
• Q(SASA): 0.9493
• 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
R/I	rs2057021551	None	0.303	N	0.474	0.111	0.226586394389	gnomAD-4.0.0	7.01908E-07	None	None	None	None	N	None	3.0434E-05	0	None	0	0	None	0	0	0	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
R/A	0.2628	likely_benign	0.2918	benign	-0.034	Destabilizing	0.016	N	0.511	neutral	None	None	None	None	N
R/C	0.2468	likely_benign	0.2718	benign	-0.365	Destabilizing	0.869	D	0.391	neutral	None	None	None	None	N
R/D	0.5861	likely_pathogenic	0.6357	pathogenic	-0.35	Destabilizing	0.075	N	0.567	neutral	None	None	None	None	N
R/E	0.31	likely_benign	0.3437	ambiguous	-0.32	Destabilizing	0.016	N	0.429	neutral	None	None	None	None	N
R/F	0.4133	ambiguous	0.4384	ambiguous	-0.391	Destabilizing	0.637	D	0.439	neutral	None	None	None	None	N
R/G	0.2427	likely_benign	0.2522	benign	-0.148	Destabilizing	0.058	N	0.545	neutral	N	0.466796447	None	None	N
R/H	0.1251	likely_benign	0.1369	benign	-0.601	Destabilizing	0.366	N	0.505	neutral	None	None	None	None	N
R/I	0.2008	likely_benign	0.2197	benign	0.219	Stabilizing	0.303	N	0.474	neutral	N	0.473213667	None	None	N
R/K	0.056	likely_benign	0.0604	benign	-0.285	Destabilizing	None	N	0.181	neutral	N	0.404224003	None	None	N
R/L	0.169	likely_benign	0.1861	benign	0.219	Stabilizing	0.075	N	0.545	neutral	None	None	None	None	N
R/M	0.2114	likely_benign	0.2221	benign	-0.173	Destabilizing	0.637	D	0.48	neutral	None	None	None	None	N
R/N	0.4167	ambiguous	0.4557	ambiguous	-0.233	Destabilizing	0.075	N	0.501	neutral	None	None	None	None	N
R/P	0.3011	likely_benign	0.3144	benign	0.151	Stabilizing	0.141	N	0.579	neutral	None	None	None	None	N
R/Q	0.1017	likely_benign	0.1106	benign	-0.255	Destabilizing	0.039	N	0.505	neutral	None	None	None	None	N
R/S	0.3594	ambiguous	0.3984	ambiguous	-0.388	Destabilizing	0.012	N	0.499	neutral	N	0.459502475	None	None	N
R/T	0.1948	likely_benign	0.2123	benign	-0.264	Destabilizing	0.058	N	0.525	neutral	N	0.459590113	None	None	N
R/V	0.2268	likely_benign	0.2595	benign	0.151	Stabilizing	0.075	N	0.559	neutral	None	None	None	None	N
R/W	0.2322	likely_benign	0.2239	benign	-0.597	Destabilizing	0.869	D	0.391	neutral	None	None	None	None	N
R/Y	0.3492	ambiguous	0.3627	ambiguous	-0.203	Destabilizing	0.366	N	0.547	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.