TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8433	25522;25523;25524	chr2:178717577;178717576;178717575	chr2:179582304;179582303;179582302
N2AB	8116	24571;24572;24573	chr2:178717577;178717576;178717575	chr2:179582304;179582303;179582302
N2A	7189	21790;21791;21792	chr2:178717577;178717576;178717575	chr2:179582304;179582303;179582302
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-69
• Domain position: 74
• Structural Position: 157
• Q(SASA): 0.207
• 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
S/C	None	None	0.998	N	0.551	0.335	0.421550847248	gnomAD-4.0.0	6.84549E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99721E-07	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
S/A	0.092	likely_benign	0.0946	benign	-0.985	Destabilizing	0.037	N	0.378	neutral	N	0.504390076	None	None	N
S/C	0.1658	likely_benign	0.1567	benign	-0.709	Destabilizing	0.998	D	0.551	neutral	N	0.484175527	None	None	N
S/D	0.549	ambiguous	0.5321	ambiguous	-1.227	Destabilizing	0.884	D	0.501	neutral	None	None	None	None	N
S/E	0.554	ambiguous	0.545	ambiguous	-1.074	Destabilizing	0.687	D	0.447	neutral	None	None	None	None	N
S/F	0.1681	likely_benign	0.1572	benign	-1.006	Destabilizing	0.063	N	0.564	neutral	N	0.487017823	None	None	N
S/G	0.1699	likely_benign	0.1669	benign	-1.336	Destabilizing	0.853	D	0.443	neutral	None	None	None	None	N
S/H	0.3082	likely_benign	0.282	benign	-1.663	Destabilizing	0.995	D	0.559	neutral	None	None	None	None	N
S/I	0.1285	likely_benign	0.1278	benign	-0.108	Destabilizing	0.934	D	0.545	neutral	None	None	None	None	N
S/K	0.6535	likely_pathogenic	0.6313	pathogenic	-0.238	Destabilizing	0.276	N	0.285	neutral	None	None	None	None	N
S/L	0.0928	likely_benign	0.0949	benign	-0.108	Destabilizing	0.855	D	0.555	neutral	None	None	None	None	N
S/M	0.1844	likely_benign	0.1802	benign	-0.053	Destabilizing	0.995	D	0.563	neutral	None	None	None	None	N
S/N	0.1789	likely_benign	0.1764	benign	-0.796	Destabilizing	0.472	N	0.507	neutral	None	None	None	None	N
S/P	0.9513	likely_pathogenic	0.9408	pathogenic	-0.368	Destabilizing	0.921	D	0.543	neutral	N	0.501772803	None	None	N
S/Q	0.464	ambiguous	0.4473	ambiguous	-0.696	Destabilizing	0.526	D	0.382	neutral	None	None	None	None	N
S/R	0.5197	ambiguous	0.4877	ambiguous	-0.483	Destabilizing	0.276	N	0.432	neutral	None	None	None	None	N
S/T	0.0699	likely_benign	0.0702	benign	-0.579	Destabilizing	0.009	N	0.286	neutral	N	0.409882404	None	None	N
S/V	0.1449	likely_benign	0.1485	benign	-0.368	Destabilizing	0.057	N	0.501	neutral	None	None	None	None	N
S/W	0.379	ambiguous	0.3318	benign	-1.142	Destabilizing	1.0	D	0.614	neutral	None	None	None	None	N
S/Y	0.1881	likely_benign	0.1746	benign	-0.736	Destabilizing	0.974	D	0.593	neutral	N	0.502736637	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.