ClinVar Miner

Submissions for variant NM_203290.4(POLR1C):c.88C>T (p.Pro30Ser)

gnomAD frequency: 0.00001  dbSNP: rs1057519455
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
MyeliNeuroGene Lab, McGill University Health Center Research Institute RCV000416459 SCV000924588 pathogenic Hypomyelinating leukodystrophy 11 criteria provided, single submitter research
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute RCV000416459 SCV002557190 likely pathogenic Hypomyelinating leukodystrophy 11 2022-02-02 criteria provided, single submitter clinical testing Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Likely Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with Treacher Collins syndrome 3 (MIM#248390) and Leukodystrophy, hypomyelinating, 11 (MIM#616494). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from proline to serine. (I) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD <0.01 for a recessive condition (v3: 1 heterozygote, 0 homozygotes). (SP) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (SP) 0604 - Variant is not located in an established domain, motif, hotspot or informative constraint region. (I) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0802 - This variant has moderate previous evidence of pathogenicity in unrelated individuals. It has been identified in at least two unrelated individuals with leukodystrophy and one family with syndromic developmental delay and intellectual disability; and cardiac phenotypes, leading to a dual diagnosis of SCN1B-related disorder. All affected individuals presented with childhood-onset (PMID: 28327206, 32042905). (SP) 0902 - This variant has moderate evidence for segregation with disease. It was found in two pairs of sibships, one with leukodrystrophy and the other with syndromic developmental delay and intellectual disability (PMID: 28327206, 32042905). (SP) 1007 - No published functional evidence has been identified for this variant. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign
Eurofins-Biomnis RCV000416459 SCV003935108 likely pathogenic Hypomyelinating leukodystrophy 11 2022-10-04 criteria provided, single submitter clinical testing
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine RCV000416459 SCV000494197 pathogenic Hypomyelinating leukodystrophy 11 no assertion criteria provided research This variant was identified in individual with developmental delay, intellectual disability, polymicrogyria, cardiomyopathy, and nystagmus. Dual molecular diagnoses involving POLR1C and SCN1B were identified.
Baylor Genetics RCV000850585 SCV000992807 uncertain significance Treacher Collins syndrome 3; Hypomyelinating leukodystrophy 11 2017-12-31 flagged submission clinical testing

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