TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31127	93604;93605;93606	chr2:178548247;178548246;178548245	chr2:179412974;179412973;179412972
N2AB	29486	88681;88682;88683	chr2:178548247;178548246;178548245	chr2:179412974;179412973;179412972
N2A	28559	85900;85901;85902	chr2:178548247;178548246;178548245	chr2:179412974;179412973;179412972
N2B	22062	66409;66410;66411	chr2:178548247;178548246;178548245	chr2:179412974;179412973;179412972
Novex-1	22187	66784;66785;66786	chr2:178548247;178548246;178548245	chr2:179412974;179412973;179412972
Novex-2	22254	66985;66986;66987	chr2:178548247;178548246;178548245	chr2:179412974;179412973;179412972
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-115
• Domain position: 15
• Structural Position: 17
• Q(SASA): 0.4996
• 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
K/R	rs1172489914	-0.007	0.006	N	0.202	0.074	0.224531998449	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
K/R	rs1172489914	-0.007	0.006	N	0.202	0.074	0.224531998449	gnomAD-4.0.0	1.5911E-06	None	None	None	None	N	None	0	2.28645E-05	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
K/A	0.1991	likely_benign	0.2025	benign	-0.074	Destabilizing	0.329	N	0.457	neutral	None	None	None	None	N
K/C	0.5239	ambiguous	0.5861	pathogenic	-0.216	Destabilizing	0.995	D	0.497	neutral	None	None	None	None	N
K/D	0.3808	ambiguous	0.3888	ambiguous	0.189	Stabilizing	0.007	N	0.189	neutral	None	None	None	None	N
K/E	0.1714	likely_benign	0.1644	benign	0.183	Stabilizing	0.27	N	0.39	neutral	N	0.501989197	None	None	N
K/F	0.6777	likely_pathogenic	0.6937	pathogenic	-0.387	Destabilizing	0.981	D	0.531	neutral	None	None	None	None	N
K/G	0.2617	likely_benign	0.2737	benign	-0.256	Destabilizing	0.495	N	0.504	neutral	None	None	None	None	N
K/H	0.2401	likely_benign	0.2705	benign	-0.609	Destabilizing	0.944	D	0.456	neutral	None	None	None	None	N
K/I	0.3456	ambiguous	0.357	ambiguous	0.322	Stabilizing	0.927	D	0.551	neutral	N	0.50027314	None	None	N
K/L	0.3135	likely_benign	0.3105	benign	0.322	Stabilizing	0.704	D	0.496	neutral	None	None	None	None	N
K/M	0.2459	likely_benign	0.2438	benign	0.3	Stabilizing	0.981	D	0.445	neutral	None	None	None	None	N
K/N	0.2751	likely_benign	0.2917	benign	0.316	Stabilizing	0.01	N	0.068	neutral	N	0.509475316	None	None	N
K/P	0.3724	ambiguous	0.3549	ambiguous	0.217	Stabilizing	0.944	D	0.476	neutral	None	None	None	None	N
K/Q	0.115	likely_benign	0.122	benign	0.066	Stabilizing	0.642	D	0.401	neutral	N	0.475229898	None	None	N
K/R	0.0699	likely_benign	0.0741	benign	0.075	Stabilizing	0.006	N	0.202	neutral	N	0.497239525	None	None	N
K/S	0.2353	likely_benign	0.2426	benign	-0.246	Destabilizing	0.037	N	0.066	neutral	None	None	None	None	N
K/T	0.1624	likely_benign	0.1614	benign	-0.105	Destabilizing	0.473	N	0.428	neutral	N	0.469745715	None	None	N
K/V	0.2896	likely_benign	0.2917	benign	0.217	Stabilizing	0.828	D	0.503	neutral	None	None	None	None	N
K/W	0.7102	likely_pathogenic	0.7353	pathogenic	-0.349	Destabilizing	0.995	D	0.627	neutral	None	None	None	None	N
K/Y	0.5132	ambiguous	0.5479	ambiguous	0.024	Stabilizing	0.981	D	0.501	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.