ClinVar Miner

Submissions for variant NM_000272.4(NPHP1):c.232T>C (p.Tyr78His) (rs140446520)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000153590 SCV000203129 likely benign not specified 2018-05-25 criteria provided, single submitter clinical testing
Invitae RCV000195676 SCV000254520 likely benign Nephronophthisis 2019-12-31 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000372811 SCV000415929 uncertain significance Senior-Loken syndrome 1 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Clinical Services Laboratory,Illumina RCV001094558 SCV000415930 uncertain significance Nephronophthisis 1 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Clinical Services Laboratory,Illumina RCV000338020 SCV000415931 uncertain significance Joubert syndrome 4 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
GeneDx RCV000153590 SCV000572850 uncertain significance not specified 2017-02-03 criteria provided, single submitter clinical testing The Y78H variant in the NPHP1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The Y78H variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. However, the Y78H variant is observed in 133/66668 (0.19%) alleles from individuals of non-Finnish European background, including one homozygote, in the ExAC dataset (Lek et al., 2016). Therefore, we interpret Y78H as a variant of uncertain significance.
Fulgent Genetics,Fulgent Genetics RCV000515315 SCV000611414 uncertain significance Joubert syndrome 4; Nephronophthisis 1; Senior-Loken syndrome 1 2017-05-23 criteria provided, single submitter clinical testing
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV001197375 SCV001368095 uncertain significance Reduced visual acuity; Macular dystrophy; Progressive cone degeneration 2019-04-30 criteria provided, single submitter clinical testing This variant was classified as: Uncertain significance. The available evidence favors the pathogenic nature of this variant, however the currently available data is insufficient to conclusively support its pathogenic nature. Thus this variant is classified as Uncertain significance - favor pathogenic. The following ACMG criteria were applied in classifying this variant: PM2,PP3,PP4. This variant was detected in heterozygous state.

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