TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16081	48466;48467;48468	chr2:178616550;178616549;178616548	chr2:179481277;179481276;179481275
N2AB	14440	43543;43544;43545	chr2:178616550;178616549;178616548	chr2:179481277;179481276;179481275
N2A	13513	40762;40763;40764	chr2:178616550;178616549;178616548	chr2:179481277;179481276;179481275
N2B	7016	21271;21272;21273	chr2:178616550;178616549;178616548	chr2:179481277;179481276;179481275
Novex-1	7141	21646;21647;21648	chr2:178616550;178616549;178616548	chr2:179481277;179481276;179481275
Novex-2	7208	21847;21848;21849	chr2:178616550;178616549;178616548	chr2:179481277;179481276;179481275
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: Fn3-4
• Domain position: 27
• Structural Position: 29
• Q(SASA): 0.6634
• 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/G	None	None	0.27	D	0.353	0.28	0.276898752692	gnomAD-4.0.0	1.59394E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86352E-06	0	0
D/N	None	None	0.002	N	0.059	0.1	0.184867976434	gnomAD-4.0.0	4.8013E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.25002E-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	0.3549	ambiguous	0.4859	ambiguous	-0.226	Destabilizing	0.27	N	0.356	neutral	N	0.461720439	None	None	N
D/C	0.6175	likely_pathogenic	0.7767	pathogenic	0.36	Stabilizing	0.995	D	0.345	neutral	None	None	None	None	N
D/E	0.3283	likely_benign	0.4246	ambiguous	-0.32	Destabilizing	0.27	N	0.245	neutral	N	0.468683109	None	None	N
D/F	0.5843	likely_pathogenic	0.7065	pathogenic	-0.514	Destabilizing	0.944	D	0.399	neutral	None	None	None	None	N
D/G	0.3938	ambiguous	0.5199	ambiguous	-0.393	Destabilizing	0.27	N	0.353	neutral	D	0.530333355	None	None	N
D/H	0.2559	likely_benign	0.4089	ambiguous	-0.597	Destabilizing	0.002	N	0.109	neutral	N	0.479234529	None	None	N
D/I	0.4577	ambiguous	0.5925	pathogenic	0.156	Stabilizing	0.944	D	0.422	neutral	None	None	None	None	N
D/K	0.5764	likely_pathogenic	0.7211	pathogenic	0.425	Stabilizing	0.003	N	0.124	neutral	None	None	None	None	N
D/L	0.5092	ambiguous	0.63	pathogenic	0.156	Stabilizing	0.704	D	0.459	neutral	None	None	None	None	N
D/M	0.71	likely_pathogenic	0.8012	pathogenic	0.513	Stabilizing	0.981	D	0.36	neutral	None	None	None	None	N
D/N	0.1054	likely_benign	0.1334	benign	0.28	Stabilizing	0.002	N	0.059	neutral	N	0.469296325	None	None	N
D/P	0.9537	likely_pathogenic	0.9746	pathogenic	0.05	Stabilizing	0.828	D	0.402	neutral	None	None	None	None	N
D/Q	0.5346	ambiguous	0.6838	pathogenic	0.282	Stabilizing	0.704	D	0.236	neutral	None	None	None	None	N
D/R	0.5896	likely_pathogenic	0.724	pathogenic	0.352	Stabilizing	0.543	D	0.441	neutral	None	None	None	None	N
D/S	0.1989	likely_benign	0.2704	benign	0.189	Stabilizing	0.037	N	0.067	neutral	None	None	None	None	N
D/T	0.3613	ambiguous	0.4832	ambiguous	0.314	Stabilizing	0.329	N	0.341	neutral	None	None	None	None	N
D/V	0.3304	likely_benign	0.4471	ambiguous	0.05	Stabilizing	0.784	D	0.471	neutral	N	0.499826492	None	None	N
D/W	0.8999	likely_pathogenic	0.939	pathogenic	-0.496	Destabilizing	0.995	D	0.368	neutral	None	None	None	None	N
D/Y	0.2238	likely_benign	0.3369	benign	-0.305	Destabilizing	0.863	D	0.441	neutral	N	0.470505953	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.