TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14294	43105;43106;43107	chr2:178633479;178633478;178633477	chr2:179498206;179498205;179498204
N2AB	12653	38182;38183;38184	chr2:178633479;178633478;178633477	chr2:179498206;179498205;179498204
N2A	11726	35401;35402;35403	chr2:178633479;178633478;178633477	chr2:179498206;179498205;179498204
N2B	5229	15910;15911;15912	chr2:178633479;178633478;178633477	chr2:179498206;179498205;179498204
Novex-1	5354	16285;16286;16287	chr2:178633479;178633478;178633477	chr2:179498206;179498205;179498204
Novex-2	5421	16486;16487;16488	chr2:178633479;178633478;178633477	chr2:179498206;179498205;179498204
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: Ig-93
• Domain position: 64
• Structural Position: 148
• Q(SASA): 0.6611
• 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	None	None	0.549	N	0.362	0.071	0.154104182512	gnomAD-4.0.0	3.18461E-06	None	None	None	None	N	None	0	4.57561E-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	0.1366	likely_benign	0.1541	benign	0.056	Stabilizing	0.002	N	0.206	neutral	None	None	None	None	N
K/C	0.5962	likely_pathogenic	0.5948	pathogenic	-0.117	Destabilizing	0.977	D	0.321	neutral	None	None	None	None	N
K/D	0.2686	likely_benign	0.3192	benign	-0.045	Destabilizing	0.447	N	0.4	neutral	None	None	None	None	N
K/E	0.1188	likely_benign	0.1234	benign	-0.052	Destabilizing	0.549	D	0.312	neutral	N	0.401700593	None	None	N
K/F	0.6068	likely_pathogenic	0.5848	pathogenic	-0.231	Destabilizing	0.92	D	0.316	neutral	None	None	None	None	N
K/G	0.1739	likely_benign	0.2058	benign	-0.112	Destabilizing	0.005	N	0.249	neutral	None	None	None	None	N
K/H	0.2146	likely_benign	0.2436	benign	-0.357	Destabilizing	0.92	D	0.306	neutral	None	None	None	None	N
K/I	0.2414	likely_benign	0.2355	benign	0.417	Stabilizing	0.81	D	0.342	neutral	N	0.466415441	None	None	N
K/L	0.2088	likely_benign	0.2263	benign	0.417	Stabilizing	0.447	N	0.409	neutral	None	None	None	None	N
K/M	0.1621	likely_benign	0.163	benign	0.202	Stabilizing	0.992	D	0.307	neutral	None	None	None	None	N
K/N	0.1811	likely_benign	0.1977	benign	0.321	Stabilizing	0.016	N	0.239	neutral	N	0.448945682	None	None	N
K/P	0.4007	ambiguous	0.4179	ambiguous	0.323	Stabilizing	0.92	D	0.33	neutral	None	None	None	None	N
K/Q	0.1013	likely_benign	0.1106	benign	0.144	Stabilizing	0.896	D	0.321	neutral	N	0.448943707	None	None	N
K/R	0.0961	likely_benign	0.0936	benign	0.048	Stabilizing	0.549	D	0.362	neutral	N	0.472341142	None	None	N
K/S	0.1625	likely_benign	0.1748	benign	-0.108	Destabilizing	0.021	N	0.257	neutral	None	None	None	None	N
K/T	0.0938	likely_benign	0.1018	benign	0.019	Stabilizing	0.379	N	0.385	neutral	N	0.447751373	None	None	N
K/V	0.2167	likely_benign	0.2282	benign	0.323	Stabilizing	0.447	N	0.393	neutral	None	None	None	None	N
K/W	0.6574	likely_pathogenic	0.6406	pathogenic	-0.289	Destabilizing	0.992	D	0.437	neutral	None	None	None	None	N
K/Y	0.4937	ambiguous	0.4799	ambiguous	0.073	Stabilizing	0.972	D	0.318	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.