TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22081	66466;66467;66468	chr2:178582128;178582127;178582126	chr2:179446855;179446854;179446853
N2AB	20440	61543;61544;61545	chr2:178582128;178582127;178582126	chr2:179446855;179446854;179446853
N2A	19513	58762;58763;58764	chr2:178582128;178582127;178582126	chr2:179446855;179446854;179446853
N2B	13016	39271;39272;39273	chr2:178582128;178582127;178582126	chr2:179446855;179446854;179446853
Novex-1	13141	39646;39647;39648	chr2:178582128;178582127;178582126	chr2:179446855;179446854;179446853
Novex-2	13208	39847;39848;39849	chr2:178582128;178582127;178582126	chr2:179446855;179446854;179446853
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: Fn3-48
• Domain position: 27
• Structural Position: 29
• Q(SASA): 0.6124
• 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/H	None	None	0.427	N	0.362	0.109	0.237489013734	gnomAD-4.0.0	1.36929E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.7993E-06	0	0
D/N	None	None	None	N	0.052	0.105	0.18995819373	gnomAD-4.0.0	6.84646E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99651E-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
D/A	0.204	likely_benign	0.1637	benign	-0.166	Destabilizing	0.042	N	0.383	neutral	N	0.512803623	None	None	N
D/C	0.626	likely_pathogenic	0.4772	ambiguous	0.27	Stabilizing	0.958	D	0.416	neutral	None	None	None	None	N
D/E	0.1834	likely_benign	0.1654	benign	-0.253	Destabilizing	0.081	N	0.247	neutral	N	0.500335758	None	None	N
D/F	0.5446	ambiguous	0.4392	ambiguous	-0.311	Destabilizing	0.331	N	0.457	neutral	None	None	None	None	N
D/G	0.276	likely_benign	0.2071	benign	-0.326	Destabilizing	0.042	N	0.321	neutral	N	0.516113287	None	None	N
D/H	0.3023	likely_benign	0.22	benign	-0.189	Destabilizing	0.427	N	0.362	neutral	N	0.508032522	None	None	N
D/I	0.3985	ambiguous	0.2908	benign	0.194	Stabilizing	0.046	N	0.462	neutral	None	None	None	None	N
D/K	0.4587	ambiguous	0.3454	ambiguous	0.524	Stabilizing	0.124	N	0.347	neutral	None	None	None	None	N
D/L	0.4353	ambiguous	0.3463	ambiguous	0.194	Stabilizing	0.124	N	0.421	neutral	None	None	None	None	N
D/M	0.5999	likely_pathogenic	0.5034	ambiguous	0.382	Stabilizing	0.497	N	0.426	neutral	None	None	None	None	N
D/N	0.098	likely_benign	0.0847	benign	0.332	Stabilizing	None	N	0.052	neutral	N	0.443154324	None	None	N
D/P	0.947	likely_pathogenic	0.9124	pathogenic	0.095	Stabilizing	0.667	D	0.383	neutral	None	None	None	None	N
D/Q	0.3726	ambiguous	0.2929	benign	0.333	Stabilizing	0.497	N	0.301	neutral	None	None	None	None	N
D/R	0.5179	ambiguous	0.3656	ambiguous	0.556	Stabilizing	0.497	N	0.433	neutral	None	None	None	None	N
D/S	0.1194	likely_benign	0.1045	benign	0.239	Stabilizing	0.002	N	0.065	neutral	None	None	None	None	N
D/T	0.2208	likely_benign	0.1818	benign	0.361	Stabilizing	0.055	N	0.305	neutral	None	None	None	None	N
D/V	0.2336	likely_benign	0.1762	benign	0.095	Stabilizing	0.001	N	0.35	neutral	N	0.479558311	None	None	N
D/W	0.8861	likely_pathogenic	0.8162	pathogenic	-0.248	Destabilizing	0.883	D	0.435	neutral	None	None	None	None	N
D/Y	0.2226	likely_benign	0.1606	benign	-0.081	Destabilizing	0.002	N	0.368	neutral	N	0.461972158	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.