TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16221	48886;48887;48888	chr2:178614946;178614945;178614944	chr2:179479673;179479672;179479671
N2AB	14580	43963;43964;43965	chr2:178614946;178614945;178614944	chr2:179479673;179479672;179479671
N2A	13653	41182;41183;41184	chr2:178614946;178614945;178614944	chr2:179479673;179479672;179479671
N2B	7156	21691;21692;21693	chr2:178614946;178614945;178614944	chr2:179479673;179479672;179479671
Novex-1	7281	22066;22067;22068	chr2:178614946;178614945;178614944	chr2:179479673;179479672;179479671
Novex-2	7348	22267;22268;22269	chr2:178614946;178614945;178614944	chr2:179479673;179479672;179479671
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-5
• Domain position: 67
• Structural Position: 99
• Q(SASA): 0.6323
• 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
E/D	rs2057034517	None	0.994	D	0.536	0.263	0.322786055943	gnomAD-4.0.0	1.6324E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.92767E-06	0	0
E/K	None	None	0.994	N	0.615	0.314	0.491455083755	gnomAD-4.0.0	1.38346E-06	None	None	None	None	N	None	6.01685E-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
E/A	0.1251	likely_benign	0.1441	benign	-0.418	Destabilizing	0.989	D	0.487	neutral	N	0.477746392	None	None	N
E/C	0.9128	likely_pathogenic	0.9325	pathogenic	0.031	Stabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
E/D	0.2971	likely_benign	0.362	ambiguous	-0.396	Destabilizing	0.994	D	0.536	neutral	D	0.554596106	None	None	N
E/F	0.9061	likely_pathogenic	0.9385	pathogenic	-0.36	Destabilizing	1.0	D	0.668	neutral	None	None	None	None	N
E/G	0.3217	likely_benign	0.375	ambiguous	-0.615	Destabilizing	0.217	N	0.303	neutral	D	0.61218926	None	None	N
E/H	0.6749	likely_pathogenic	0.7585	pathogenic	-0.2	Destabilizing	1.0	D	0.613	neutral	None	None	None	None	N
E/I	0.4376	ambiguous	0.5016	ambiguous	0.068	Stabilizing	1.0	D	0.684	prob.neutral	None	None	None	None	N
E/K	0.1589	likely_benign	0.1851	benign	0.336	Stabilizing	0.994	D	0.615	neutral	N	0.50399125	None	None	N
E/L	0.5635	ambiguous	0.6309	pathogenic	0.068	Stabilizing	1.0	D	0.657	neutral	None	None	None	None	N
E/M	0.5532	ambiguous	0.6093	pathogenic	0.237	Stabilizing	1.0	D	0.617	neutral	None	None	None	None	N
E/N	0.3801	ambiguous	0.463	ambiguous	0.031	Stabilizing	0.999	D	0.649	neutral	None	None	None	None	N
E/P	0.3388	likely_benign	0.3628	ambiguous	-0.074	Destabilizing	1.0	D	0.571	neutral	None	None	None	None	N
E/Q	0.1679	likely_benign	0.1912	benign	0.054	Stabilizing	0.999	D	0.679	prob.neutral	N	0.506494362	None	None	N
E/R	0.3106	likely_benign	0.3515	ambiguous	0.491	Stabilizing	1.0	D	0.641	neutral	None	None	None	None	N
E/S	0.2727	likely_benign	0.3366	benign	-0.126	Destabilizing	0.992	D	0.6	neutral	None	None	None	None	N
E/T	0.2615	likely_benign	0.3197	benign	0.034	Stabilizing	0.999	D	0.567	neutral	None	None	None	None	N
E/V	0.2366	likely_benign	0.28	benign	-0.074	Destabilizing	0.999	D	0.608	neutral	D	0.558442736	None	None	N
E/W	0.9768	likely_pathogenic	0.9834	pathogenic	-0.22	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
E/Y	0.8423	likely_pathogenic	0.8881	pathogenic	-0.117	Destabilizing	1.0	D	0.624	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.