Table 2. Novel MTM1 mutations submitted to the MTM1-LOVD.
| Patient ID | DNA mutation | Gene location | Type of mutation | cDNA effect | Protein effect | Origin of mutation | Phenotype | Geographic origin |
|---|---|---|---|---|---|---|---|---|
| 18914 | c.=/(?_-76)_342 +?dup | Exons 1–5 | Large duplication | r.[=, 343_444del] | p.Asp115_Leu148del | De novo, somatic | Mild | Portugal |
| 10959 | c.63+834_1645-2104del | Intron 2–15 | Large deletion | r.(?) | p.(Thr22_Gln548del) | Inherited (MC) | Severe | United Kingdom |
| 24703 | c.2T>A | Exon 2 | Affects initiation codon | r.(?) | p.0? | Inherited (de novo, in mother) | Severe (at birth) | Germany |
| 21000 | c.32C>A | Exon 2 | Nonsense | r.(?) | p.(Ser11*) | de novo | Severe | Germany |
| 24706 | c.231+1G>T | Intron 4 | Donor splice site disruptiona | r.(spl?) | p.(?) | Inherited (MGC) | Severe (died at 10 months) | Germany |
| 20980 | c.323G>A | Exon 5 | Missense | r.(?) | p.(Gly108Asp)b | de novo | Mild (24 years old, still walking) | Germany |
| 18861 | c.342+5G>A | Intron 5 | Donor splice site disruption | r.232_342del | p.Ser79_Asp115del | Inherited (MC) | Severe | Germany |
| 20960 | c.469G>T | Exon 7 | Nonsense | r.(?) | p.(Glu157*) | Inherited (MC) | Severe | United Kingdom |
| 20961 | c.509_528dup | Exon 7 | Out-of-frame duplication | r.(?) | p.(Gly177Trpfs*16) | Unknown | Severe (long-term survivor) | Germany |
| 20933 | c.595C>A | Exon 8 | Missense | r.(?) | p.(Pro199Thr)b | Inherited (MC) | Unknown (neonatal death) | Portugal |
| 24711 | c.596dup | Exon 8 | Out-of-frame duplication | r.(?) | p.(Ala200Cysfs*12) | Inherited (MC) | Severe | Germany |
| 24702 | c.637C>T | Exon 8 | Missense | r.(?) | p.(Leu213Phe)b | Inherited (MC) | Mild (diagnosed at 24 years of age) | Germany |
| 24707 | c.659G>C | Exon 8 | Missense | r.(?) | p.(Arg220Thr)b | Unknown | Severe (at birth) | Germany/Albania |
| 20951 | c.765_767delinsGG | Exon 9 | Out-of-frame deletion | r.(?) | p.(Asp256Valfs*28) | Inherited (MC) | Severe | Turkey |
| 11124 | c.867+1G>A | Intron 9 | Donor splice site disruptiona | r.(spl?) | p.(?) | Inherited (MC) | Unknown | Portugal |
| 16734 | c.1088_1089del | Exon 11 | Out-of-frame deletion | r.(?) | p.(Lys363Serfs*14) | Inherited (MC) | Severe | Germany |
| 11170 | c.1241T>C | Exon 11 | Missense | r.(?) | p.(Phe414Ser)b | Unknown | Unknown | Portugal |
| 12852 | c.1247A>G | Exon 11 | Missense | r.(?) | p.(His416Arg)b | Unknown | Severe | Germany |
| 20944 | c.1318C>T | Exon 12 | Nonsense | r.(?) | p.(Gln440*) | Inherited (MC) | Severe | Germany |
| 20955 | c.1319_1321delinsTA | Exon 12 | Out-of-frame deletion/insertion | r.(?) | p.(Gln440Leufs*24) | Inherited (MC) | Severe | Germany |
| 24712 | c.1328_1331del | Exon 12 | Out-of-frame deletion | r.(?) | p.(Asp443Valfs*20) | Unknown | Severe | Germany |
| 14208 | c.1388_1389ins376, GenBank JQ403527 | Exon 13 | In-frame exon skipping | r.1354_1467del | p.Phe452_Gln489del | Inherited (de novo, in mother) | Severe | Turkey |
| 20938 | c.1509_1510del | Exon 14 | Out-of-frame deletion | r.(?) | p.(Asn503Lysfs*2) | Unknown | Severe | United Kingdom |
| 20952 | c.1519_1522del | Exon 14 | Out-of-frame deletion | r.(?) | p.(Glu507Asnfs*28) | Inherited (MC) | Severe | Germany |
| 24705 | c.1600T>C | Exon 14 | Missense | r.(?) | p.(Trp534Arg)b | Inherited (MGC) | Severe (at birth) | Germany |
Abbreviations: ID, patient identification in database; MC, mother carrier; MGC, maternal grandmother carrier.
Variants are described according to the reference sequence NM_000252.2, using HGVS nomenclature guidelines.
a
Predicted to affect splicing by bioinformatic analysis.
b
Pathogenicity assessment of missense variants in Supplementary Information (S3).