TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22987	69184;69185;69186	chr2:178577376;178577375;178577374	chr2:179442103;179442102;179442101
N2AB	21346	64261;64262;64263	chr2:178577376;178577375;178577374	chr2:179442103;179442102;179442101
N2A	20419	61480;61481;61482	chr2:178577376;178577375;178577374	chr2:179442103;179442102;179442101
N2B	13922	41989;41990;41991	chr2:178577376;178577375;178577374	chr2:179442103;179442102;179442101
Novex-1	14047	42364;42365;42366	chr2:178577376;178577375;178577374	chr2:179442103;179442102;179442101
Novex-2	14114	42565;42566;42567	chr2:178577376;178577375;178577374	chr2:179442103;179442102;179442101
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-128
• Domain position: 38
• Structural Position: 56
• Q(SASA): 0.7207
• 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/N	rs749120610	0.375	0.904	N	0.545	0.213	0.266843984389	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	1.68067E-04	None	0	None	0	0	0
D/N	rs749120610	0.375	0.904	N	0.545	0.213	0.266843984389	gnomAD-4.0.0	1.27391E-05	None	None	None	None	N	None	0	0	None	0	2.22408E-04	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
D/A	0.1408	likely_benign	0.1238	benign	-0.255	Destabilizing	0.822	D	0.528	neutral	N	0.45057702	None	None	N
D/C	0.516	ambiguous	0.4588	ambiguous	0.138	Stabilizing	0.998	D	0.661	neutral	None	None	None	None	N
D/E	0.1036	likely_benign	0.0911	benign	-0.252	Destabilizing	0.025	N	0.199	neutral	N	0.387237618	None	None	N
D/F	0.4242	ambiguous	0.3724	ambiguous	-0.28	Destabilizing	0.915	D	0.612	neutral	None	None	None	None	N
D/G	0.1653	likely_benign	0.1507	benign	-0.426	Destabilizing	0.904	D	0.529	neutral	N	0.501083199	None	None	N
D/H	0.2472	likely_benign	0.2158	benign	-0.146	Destabilizing	0.942	D	0.547	neutral	N	0.506835735	None	None	N
D/I	0.1984	likely_benign	0.1622	benign	0.143	Stabilizing	0.956	D	0.617	neutral	None	None	None	None	N
D/K	0.3226	likely_benign	0.2836	benign	0.455	Stabilizing	0.86	D	0.551	neutral	None	None	None	None	N
D/L	0.2615	likely_benign	0.2292	benign	0.143	Stabilizing	0.915	D	0.538	neutral	None	None	None	None	N
D/M	0.4179	ambiguous	0.3569	ambiguous	0.301	Stabilizing	0.998	D	0.631	neutral	None	None	None	None	N
D/N	0.0989	likely_benign	0.0868	benign	0.172	Stabilizing	0.904	D	0.545	neutral	N	0.475782109	None	None	N
D/P	0.4169	ambiguous	0.3667	ambiguous	0.032	Stabilizing	0.993	D	0.537	neutral	None	None	None	None	N
D/Q	0.2649	likely_benign	0.2373	benign	0.197	Stabilizing	0.956	D	0.467	neutral	None	None	None	None	N
D/R	0.3852	ambiguous	0.3412	ambiguous	0.523	Stabilizing	0.956	D	0.577	neutral	None	None	None	None	N
D/S	0.1352	likely_benign	0.1181	benign	0.092	Stabilizing	0.86	D	0.5	neutral	None	None	None	None	N
D/T	0.1796	likely_benign	0.1524	benign	0.23	Stabilizing	0.926	D	0.539	neutral	None	None	None	None	N
D/V	0.1259	likely_benign	0.108	benign	0.032	Stabilizing	0.942	D	0.546	neutral	N	0.461236731	None	None	N
D/W	0.8226	likely_pathogenic	0.8014	pathogenic	-0.172	Destabilizing	0.994	D	0.649	neutral	None	None	None	None	N
D/Y	0.1621	likely_benign	0.1512	benign	-0.046	Destabilizing	0.032	N	0.399	neutral	N	0.490386202	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.