TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30394	91405;91406;91407	chr2:178551720;178551719;178551718	chr2:179416447;179416446;179416445
N2AB	28753	86482;86483;86484	chr2:178551720;178551719;178551718	chr2:179416447;179416446;179416445
N2A	27826	83701;83702;83703	chr2:178551720;178551719;178551718	chr2:179416447;179416446;179416445
N2B	21329	64210;64211;64212	chr2:178551720;178551719;178551718	chr2:179416447;179416446;179416445
Novex-1	21454	64585;64586;64587	chr2:178551720;178551719;178551718	chr2:179416447;179416446;179416445
Novex-2	21521	64786;64787;64788	chr2:178551720;178551719;178551718	chr2:179416447;179416446;179416445
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-109
• Domain position: 71
• Structural Position: 103
• Q(SASA): 0.2235
• 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
D/E	None	None	0.198	N	0.237	0.132	0.12205267543	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	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
D/A	0.3184	likely_benign	0.354	ambiguous	-0.562	Destabilizing	0.978	D	0.577	neutral	N	0.429457095	None	None	N
D/C	0.7765	likely_pathogenic	0.8179	pathogenic	-0.078	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
D/E	0.2572	likely_benign	0.2666	benign	-0.459	Destabilizing	0.198	N	0.237	neutral	N	0.316131589	None	None	N
D/F	0.774	likely_pathogenic	0.798	pathogenic	-0.032	Destabilizing	0.999	D	0.774	deleterious	None	None	None	None	N
D/G	0.4699	ambiguous	0.5121	ambiguous	-1.007	Destabilizing	0.989	D	0.573	neutral	N	0.46741805	None	None	N
D/H	0.5761	likely_pathogenic	0.6089	pathogenic	-0.251	Destabilizing	1.0	D	0.672	neutral	N	0.501261265	None	None	N
D/I	0.6298	likely_pathogenic	0.6697	pathogenic	0.661	Stabilizing	0.999	D	0.788	deleterious	None	None	None	None	N
D/K	0.8294	likely_pathogenic	0.8413	pathogenic	-0.479	Destabilizing	0.983	D	0.532	neutral	None	None	None	None	N
D/L	0.6268	likely_pathogenic	0.64	pathogenic	0.661	Stabilizing	0.998	D	0.751	deleterious	None	None	None	None	N
D/M	0.8097	likely_pathogenic	0.8341	pathogenic	1.285	Stabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
D/N	0.2555	likely_benign	0.2839	benign	-0.932	Destabilizing	0.989	D	0.553	neutral	N	0.441884887	None	None	N
D/P	0.8404	likely_pathogenic	0.842	pathogenic	0.278	Stabilizing	0.999	D	0.675	neutral	None	None	None	None	N
D/Q	0.6031	likely_pathogenic	0.6323	pathogenic	-0.66	Destabilizing	0.995	D	0.591	neutral	None	None	None	None	N
D/R	0.8217	likely_pathogenic	0.832	pathogenic	-0.412	Destabilizing	0.995	D	0.722	prob.delet.	None	None	None	None	N
D/S	0.2665	likely_benign	0.2956	benign	-1.462	Destabilizing	0.983	D	0.47	neutral	None	None	None	None	N
D/T	0.5332	ambiguous	0.5614	ambiguous	-1.059	Destabilizing	0.998	D	0.622	neutral	None	None	None	None	N
D/V	0.4685	ambiguous	0.5125	ambiguous	0.278	Stabilizing	0.997	D	0.739	prob.delet.	N	0.42503271	None	None	N
D/W	0.9478	likely_pathogenic	0.9499	pathogenic	0.045	Stabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
D/Y	0.3856	ambiguous	0.407	ambiguous	0.236	Stabilizing	0.999	D	0.777	deleterious	N	0.477000326	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.