TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9638	29137;29138;29139	chr2:178707655;178707654;178707653	chr2:179572382;179572381;179572380
N2AB	9321	28186;28187;28188	chr2:178707655;178707654;178707653	chr2:179572382;179572381;179572380
N2A	8394	25405;25406;25407	chr2:178707655;178707654;178707653	chr2:179572382;179572381;179572380
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: F
• RefSeq wild type transcript codon: TTC
• RefSeq wild type template codon: AAG
• Domain: Ig-82
• Domain position: 49
• Structural Position: 123
• Q(SASA): 0.33
• 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
F/V	rs2076079100	None	0.002	None	0.217	0.276	0.48300943003	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
F/A	0.6794	likely_pathogenic	0.5803	pathogenic	-2.253	Highly Destabilizing	0.329	N	0.363	neutral	None	None	None	None	N
F/C	0.4176	ambiguous	0.3424	ambiguous	-1.287	Destabilizing	0.975	D	0.515	neutral	None	None	None	None	N
F/D	0.9438	likely_pathogenic	0.8901	pathogenic	-1.18	Destabilizing	0.981	D	0.591	neutral	None	None	None	None	N
F/E	0.9378	likely_pathogenic	0.8968	pathogenic	-1.06	Destabilizing	0.828	D	0.6	neutral	None	None	None	None	N
F/G	0.8799	likely_pathogenic	0.8132	pathogenic	-2.627	Highly Destabilizing	0.828	D	0.587	neutral	None	None	None	None	N
F/H	0.7373	likely_pathogenic	0.6458	pathogenic	-0.954	Destabilizing	0.981	D	0.525	neutral	None	None	None	None	N
F/I	0.1714	likely_benign	0.1466	benign	-1.108	Destabilizing	0.003	N	0.091	neutral	None	None	None	None	N
F/K	0.9267	likely_pathogenic	0.887	pathogenic	-1.384	Destabilizing	0.828	D	0.583	neutral	None	None	None	None	N
F/L	0.7258	likely_pathogenic	0.7001	pathogenic	-1.108	Destabilizing	0.002	N	0.099	neutral	None	None	None	None	N
F/M	0.4576	ambiguous	0.4646	ambiguous	-0.856	Destabilizing	0.176	N	0.244	neutral	None	None	None	None	N
F/N	0.7968	likely_pathogenic	0.7179	pathogenic	-1.494	Destabilizing	0.981	D	0.547	neutral	None	None	None	None	N
F/P	0.9843	likely_pathogenic	0.9695	pathogenic	-1.487	Destabilizing	0.981	D	0.545	neutral	None	None	None	None	N
F/Q	0.8677	likely_pathogenic	0.8081	pathogenic	-1.511	Destabilizing	0.944	D	0.527	neutral	None	None	None	None	N
F/R	0.8644	likely_pathogenic	0.7769	pathogenic	-0.819	Destabilizing	0.944	D	0.555	neutral	None	None	None	None	N
F/S	0.5596	ambiguous	0.4357	ambiguous	-2.296	Highly Destabilizing	0.784	D	0.514	neutral	None	None	None	None	N
F/T	0.6198	likely_pathogenic	0.5318	ambiguous	-2.072	Highly Destabilizing	0.704	D	0.485	neutral	None	None	None	None	N
F/V	0.1797	likely_benign	0.1561	benign	-1.487	Destabilizing	0.002	N	0.217	neutral	None	None	None	None	N
F/W	0.6567	likely_pathogenic	0.5911	pathogenic	-0.26	Destabilizing	0.995	D	0.472	neutral	None	None	None	None	N
F/Y	0.1778	likely_benign	0.157	benign	-0.532	Destabilizing	0.784	D	0.407	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.